Top

Published in:

01-12-2020 | Chronic Inflammatory Bowel Disease | Review

Involvement of dopaminergic signaling in the cross talk between the renin-angiotensin system and inflammation

Authors: Javier Campos, Rodrigo Pacheco

Published in: Seminars in Immunopathology | Issue 6/2020

Abstract

The renin-angiotensin system (RAS) is a fundamental regulator of blood pressure and has emerged as an important player in the control of inflammatory processes. Accordingly, imbalance on RAS components either systemically or locally might trigger the development of inflammatory disorders by affecting immune cells. At the same time, alterations in the dopaminergic system have been consistently involved in the physiopathology of inflammatory disorders. Accordingly, the interaction between the RAS and the dopaminergic system has been studied in the context of inflammation of the central nervous system (CNS), kidney, and intestine, where they exert antagonistic actions in the regulation of the immune system. In this review, we summarized, integrated, and discussed the cross talk of the dopaminergic system and the RAS in the regulation of inflammatory pathologies, including neurodegenerative disorders, such as Parkinson’s disease. We analyzed the molecular mechanisms underlying the interaction between both systems in the CNS and in systemic pathologies. Moreover, we also analyzed the impact of the commensal microbiota in the regulation of RAS and dopaminergic system and how it is involved in inflammatory disorders. Furthermore, we summarized the therapeutic approaches that have yielded positive results in preclinical or clinical studies regarding the use of drugs targeting the RAS and dopaminergic system for the treatment of inflammatory conditions. Further understanding of the molecular and cellular regulation of the RAS-dopaminergic cross talk should allow the formulation of new therapies consisting of novel drugs and/or repurposing already existing drugs, alone or in combination, for the treatment of inflammatory disorders.

Pahwa R, Singh A, Jialal I (2020) Chronic inflammation. In: StatPearls. Treasure Island (FL),

Suzuki Y, Ruiz-Ortega M, Gomez-Guerrero C, Tomino Y, Egido J (2003) Angiotensin II, the immune system and renal diseases: another road for RAS? Nephrol Dial Transplant 18(8):1423–1426. https://doi.org/10.1093/ndt/gfg223CrossRefPubMed

Capettini LS, Montecucco F, Mach F, Stergiopulos N, Santos RA, da Silva RF (2012) Role of renin-angiotensin system in inflammation, immunity and aging. Curr Pharm Des 18(7):963–970. https://doi.org/10.2174/138161212799436593CrossRefPubMed

Satou R, Penrose H, Navar LG (2018) Inflammation as a regulator of the renin-angiotensin system and blood pressure. Curr Hypertens Rep 20(12):100. https://doi.org/10.1007/s11906-018-0900-0CrossRefPubMedPubMedCentral

Hammer A, Stegbauer J, Linker RA (2017) Macrophages in neuroinflammation: role of the renin-angiotensin-system. Pflugers Arch 469(3-4):431–444. https://doi.org/10.1007/s00424-017-1942-xCrossRefPubMed

Vidal PM, Pacheco R (2019) Targeting the dopaminergic system in autoimmunity. J NeuroImmune Pharmacol 15:57–73. https://doi.org/10.1007/s11481-019-09834-5CrossRefPubMed

Sparks MA, Crowley SD, Gurley SB, Mirotsou M, Coffman TM (2014) Classical renin-angiotensin system in kidney physiology. Compr Physiol 4(3):1201–1228. https://doi.org/10.1002/cphy.c130040CrossRefPubMedPubMedCentral

Cerrato BD, Frasch AP, Nakagawa P, Longo-Carbajosa N, Pena C, Hocht C, Gironacci MM (2012) Angiotensin-(1-7) upregulates central nitric oxide synthase in spontaneously hypertensive rats. Brain Res 1453:1–7. https://doi.org/10.1016/j.brainres.2012.03.022CrossRefPubMed

Mecca AP, Regenhardt RW, O'Connor TE, Joseph JP, Raizada MK, Katovich MJ, Sumners C (2011) Cerebroprotection by angiotensin-(1-7) in endothelin-1-induced ischaemic stroke. Exp Physiol 96(10):1084–1096. https://doi.org/10.1113/expphysiol.2011.058578CrossRefPubMedPubMedCentral

10.

Mordwinkin NM, Meeks CJ, Jadhav SS, Espinoza T, Roda N, diZerega GS, Louie SG, Rodgers KE (2012) Angiotensin-(1-7) administration reduces oxidative stress in diabetic bone marrow. Endocrinology 153(5):2189–2197. https://doi.org/10.1210/en.2011-2031CrossRefPubMedPubMedCentral

11.

Liao Z, Chakrabarty A, Mu Y, Bhattacherjee A, Goestch M, Leclair CM, Smith PG (2017) A local inflammatory renin-angiotensin system drives sensory axon sprouting in provoked vestibulodynia. J Pain 18(5):511–525. https://doi.org/10.1016/j.jpain.2016.12.008CrossRefPubMedPubMedCentral

12.

Labandeira-Garcia JL, Rodriguez-Perez AI, Garrido-Gil P, Rodriguez-Pallares J, Lanciego JL, Guerra MJ (2017) Brain renin-angiotensin system and microglial polarization: implications for aging and neurodegeneration. Front Aging Neurosci 9:129. https://doi.org/10.3389/fnagi.2017.00129CrossRefPubMedPubMedCentral

13.

Santos CF, Morandini AC, Dionisio TJ, Faria FA, Lima MC, Figueiredo CM, Colombini-Ishikiriama BL, Sipert CR, Maciel RP, Akashi AP, Souza GP, Garlet GP, Rodini CO, Amaral SL, Becari C, Salgado MC, Oliveira EB, Matus I, Didier DN, Greene AS (2015) Functional local renin-angiotensin system in human and rat periodontal tissue. PLoS One 10(8):e0134601. https://doi.org/10.1371/journal.pone.0134601CrossRefPubMedPubMedCentral

14.

He L, Du J, Chen Y, Liu C, Zhou M, Adhikari S, Rubin DT, Pekow J, Li YC (2019) Renin-angiotensin system promotes colonic inflammation by inducing TH17 activation via JAK2/STAT pathway. Am J Physiol Gastrointest Liver Physiol 316(6):G774–G784. https://doi.org/10.1152/ajpgi.00053.2019CrossRefPubMedPubMedCentral

15.

Pacheco R (2017) Targeting dopamine receptor D3 signalling in inflammation. Oncotarget 8(5):7224–7225. https://doi.org/10.18632/oncotarget.14601CrossRefPubMedPubMedCentral

16.

Elgueta D, Aymerich MS, Contreras F, Montoya A, Celorrio M, Rojo-Bustamante E, Riquelme E, Gonzalez H, Vasquez M, Franco R, Pacheco R (2017) Pharmacologic antagonism of dopamine receptor D3 attenuates neurodegeneration and motor impairment in a mouse model of Parkinson’s disease. Neuropharmacology 113(Pt A):110–123. https://doi.org/10.1016/j.neuropharm.2016.09.028CrossRefPubMed

17.

Elgueta D, Contreras F, Prado C, Montoya A, Ugalde V, Chovar O, Villagra R, Henriquez C, Abellanas MA, Aymerich MS, Franco R, Pacheco R (2019) Dopamine receptor d3 expression is altered in cd4+ t-cells from Parkinson’s disease patients and its pharmacologic inhibition attenuates the motor impairment in a mouse model. Front Immunol 10. https://doi.org/10.3389/fimmu.2019.00981

18.

Arreola R, Alvarez-Herrera S, Perez-Sanchez G, Becerril-Villanueva E, Cruz-Fuentes C, Flores-Gutierrez EO, Garces-Alvarez ME, de la Cruz-Aguilera DL, Medina-Rivero E, Hurtado-Alvarado G, Quintero-Fabian S, Pavon L (2016) Immunomodulatory effects mediated by dopamine. J Immunol Res 2016:3160486–3160431. https://doi.org/10.1155/2016/3160486CrossRefPubMedPubMedCentral

19.

Gonzalez H, Contreras F, Pacheco R (2015) Regulation of the neurodegenerative process associated to Parkinson’s disease by CD4+ T-cells. J NeuroImmune Pharmacol 10(4):561–575. https://doi.org/10.1007/s11481-015-9618-9CrossRefPubMed

20.

Gonzalez H, Contreras F, Prado C, Elgueta D, Franz D, Bernales S, Pacheco R (2013) Dopamine receptor d3 expressed on cd4+ t cells favors neurodegeneration of dopaminergic neurons during Parkinson’s disease. J Immunol 190(10):5048–5056. https://doi.org/10.4049/jimmunol.1203121CrossRefPubMed

21.

Pacheco R, Contreras F, Zouali M (2014) The dopaminergic system in autoimmune diseases. Front Immunol 5:117. https://doi.org/10.3389/fimmu.2014.00117CrossRefPubMedPubMedCentral

22.

Contreras F, Prado C, Gonzalez H, Franz D, Osorio-Barrios F, Osorio F, Ugalde V, Lopez E, Elgueta D, Figueroa A, Lladser A, Pacheco R (2016) Dopamine receptor D3 signaling on CD4+ T cells favors Th1- and Th17-mediated immunity. J Immunol 196(10):4143–4149. https://doi.org/10.4049/jimmunol.1502420CrossRefPubMed

23.

Prado C, Bernales S, Pacheco R (2013) Modulation of T-cell mediated immunity by dopamine receptor d5. Endocr Metab Immune Disord Drug Targets 13(2):184–194CrossRefPubMed

24.

Prado C, Contreras F, Gonzalez H, Diaz P, Elgueta D, Barrientos M, Herrada AA, Lladser A, Bernales S, Pacheco R (2012) Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity. J Immunol 188(7):3062–3070. https://doi.org/10.4049/jimmunol.1103096CrossRefPubMed

25.

Prado C, Gaiazzi M, Gonzalez H, Ugalde V, Figueroa A, Osorio-Barrios FJ, Lopez E, Lladser A, Rasini E, Marino F, Zaffaroni M, Cosentino M, Pacheco R (2018) Dopaminergic stimulation of myeloid antigen-presenting cells attenuates signal transducer and activator of transcription 3-activation favouring the development of experimental autoimmune encephalomyelitis. Front Immunol 9:571. https://doi.org/10.3389/fimmu.2018.00571CrossRefPubMedPubMedCentral

26.

Cosentino M, Ferrari M, Kustrimovic N, Rasini E, Marino F (2015) Influence of dopamine receptor gene polymorphisms on circulating T lymphocytes: a pilot study in healthy subjects. Hum Immunol 76(10):747–752. https://doi.org/10.1016/j.humimm.2015.09.032CrossRefPubMed

27.

Franz D, Contreras F, Gonzalez H, Prado C, Elgueta D, Figueroa C, Pacheco R (2015) Dopamine receptors D3 and D5 regulate CD4(+)T-cell activation and differentiation by modulating ERK activation and cAMP production. J Neuroimmunol 284:18–29. https://doi.org/10.1016/j.jneuroim.2015.05.003CrossRefPubMed

28.

Osorio-Barrios F, Prado C, Contreras F, Pacheco R (2018) Dopamine receptor D5 signaling plays a dual role in experimental autoimmune encephalomyelitis potentiating Th17-mediated immunity and favoring suppressive activity of regulatory T-cells. Front Cell Neurosci 12:192. https://doi.org/10.3389/fncel.2018.00192CrossRefPubMedPubMedCentral

29.

Papa I, Saliba D, Ponzoni M, Bustamante S, Canete PF, Gonzalez-Figueroa P, McNamara HA, Valvo S, Grimbaldeston M, Sweet RA, Vohra H, Cockburn IA, Meyer-Hermann M, Dustin ML, Doglioni C, Vinuesa CG (2017) TFH-derived dopamine accelerates productive synapses in germinal centres. Nature 547(7663):318–323. https://doi.org/10.1038/nature23013CrossRefPubMedPubMedCentral

30.

Pacheco R, Prado CE, Barrientos MJ, Bernales S (2009) Role of dopamine in the physiology of T-cells and dendritic cells. J Neuroimmunol 216(1-2):8–19. https://doi.org/10.1016/j.jneuroim.2009.07.018CrossRefPubMed

31.

Cosentino M, Fietta AM, Ferrari M, Rasini E, Bombelli R, Carcano E, Saporiti F, Meloni F, Marino F, Lecchini S (2007) Human CD4 + CD25+ regulatory T cells selectively express tyrosine hydroxylase and contain endogenous catecholamines subserving an autocrine/paracrine inhibitory functional loop. Blood 109(2):632–642CrossRefPubMed

32.

Wang W, Cohen JA, Wallrapp A, Trieu KG, Barrios J, Shao F, Krishnamoorthy N, Kuchroo VK, Jones MR, Fine A, Bai Y, Ai X (2019) Age-related dopaminergic innervation augments T helper 2-type allergic inflammation in the postnatal lung. Immunity 51(6):1102–1118 e1107. https://doi.org/10.1016/j.immuni.2019.10.002CrossRefPubMedPubMedCentral

33.

Figueroa C, Gálvez-Cancino F, Oyarce C, Contreras F, Prado C, Valeria C, Cruz S, Lladser A, Pacheco R (2017) Inhibition of dopamine receptor D3 signaling in dendritic cells increases antigen cross-presentation to CD8+ T-cells favoring anti-tumor immunity. J Neuroimmunol Accepted

34.

Torres-Rosas R, Yehia G, Pena G, Mishra P, del Rocio T-BM, Moreno-Eutimio MA, Arriaga-Pizano LA, Isibasi A, Ulloa L (2014) Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat Med 20(3):291–295. https://doi.org/10.1038/nm.3479CrossRefPubMedPubMedCentral

35.

Yan Y, Jiang W, Liu L, Wang X, Ding C, Tian Z, Zhou R (2015) Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell 160(1-2):62–73. https://doi.org/10.1016/j.cell.2014.11.047CrossRefPubMed

36.

Levite M, Marino F, Cosentino M (2017) Dopamine, T cells and multiple sclerosis (MS). J Neural Transm 124(5):525–542. https://doi.org/10.1007/s00702-016-1640-4CrossRefPubMed

37.

Comi C, Ferrari M, Marino F, Magistrelli L, Cantello R, Riboldazzi G, Bianchi ML, Bono G, Cosentino M (2017) Polymorphisms of dopamine receptor genes and risk of L-dopa-induced dyskinesia in Parkinson’s disease. Int J Mol Sci 18(2). https://doi.org/10.3390/ijms18020242

38.

McGuire V, Van Den Eeden SK, Tanner CM, Kamel F, Umbach DM, Marder K, Mayeux R, Ritz B, Ross GW, Petrovitch H, Topol B, Popat RA, Costello S, Manthripragada AD, Southwick A, Myers RM, Nelson LM (2011) Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a multiethnic consortium. J Neurol Sci 307(1-2):22–29. https://doi.org/10.1016/j.jns.2011.05.031CrossRefPubMedPubMedCentral

39.

Magro F, Cunha E, Araujo F, Meireles E, Pereira P, Dinis-Ribeiro M, Veloso FT, Medeiros R, Soares-da-Silva P (2006) Dopamine D2 receptor polymorphisms in inflammatory bowel disease and the refractory response to treatment. Dig Dis Sci 51(11):2039–2044. https://doi.org/10.1007/s10620-006-9168-3CrossRefPubMed

40.

Jiang X, Konkalmatt P, Yang Y, Gildea J, Jones JE, Cuevas S, Felder RA, Jose PA, Armando I (2014) Single-nucleotide polymorphisms of the dopamine D2 receptor increase inflammation and fibrosis in human renal proximal tubule cells. Hypertension 63(3):e74–e80. https://doi.org/10.1161/HYPERTENSIONAHA.113.02569CrossRefPubMed

41.

Zhang Y, Cuevas S, Asico LD, Escano C, Yang Y, Pascua AM, Wang X, Jones JE, Grandy D, Eisner G, Jose PA, Armando I (2012) Deficient dopamine D2 receptor function causes renal inflammation independently of high blood pressure. PLoS One 7(6):e38745. https://doi.org/10.1371/journal.pone.0038745CrossRefPubMedPubMedCentral

42.

Pinoli M, Marino F, Cosentino M (2017) Dopaminergic regulation of innate immunity: a review. J Neuroimmune Pharm 12(4):602–623. https://doi.org/10.1007/s11481-017-9749-2CrossRef

43.

Beaulieu JM, Gainetdinov RR (2011) The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63(1):182–217. https://doi.org/10.1124/pr.110.002642CrossRefPubMed

44.

Magro F, Vieira-Coelho MA, Fraga S, Serrao MP, Veloso FT, Ribeiro T, Soares-da-Silva P (2002) Impaired synthesis or cellular storage of norepinephrine, dopamine, and 5-hydroxytryptamine in human inflammatory bowel disease. Dig Dis Sci 47(1):216–224CrossRefPubMed

45.

Magro F, Fraga S, Ribeiro T, Soares-da-Silva P (2004) Decreased availability of intestinal dopamine in transmural colitis may relate to inhibitory effects of interferon-gamma upon L-DOPA uptake. Acta Physiol Scand 180(4):379–386. https://doi.org/10.1111/j.1365-201X.2004.01260.xCrossRefPubMed

46.

Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S (2009) Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest 119(1):182–192PubMed

47.

McKenna F, McLaughlin PJ, Lewis BJ, Sibbring GC, Cummerson JA, Bowen-Jones D, Moots RJ (2002) Dopamine receptor expression on human T- and B-lymphocytes, monocytes, neutrophils, eosinophils and NK cells: a flow cytometric study. J Neuroimmunol 132(1-2):34–40CrossRefPubMed

48.

Kipnis J, Cardon M, Avidan H, Lewitus GM, Mordechay S, Rolls A, Shani Y, Schwartz M (2004) Dopamine, through the extracellular signal-regulated kinase pathway, downregulates CD4 + CD25+ regulatory T-cell activity: implications for neurodegeneration. J Neurosci 24(27):6133–6143CrossRefPubMedPubMedCentral

49.

Watanabe Y, Nakayama T, Nagakubo D, Hieshima K, Jin Z, Katou F, Hashimoto K, Yoshie O (2006) Dopamine selectively induces migration and homing of naive CD8+ T cells via dopamine receptor D3. J Immunol 176(2):848–856CrossRefPubMed

50.

Coley JS, Calderon TM, Gaskill PJ, Eugenin EA, Berman JW (2015) Dopamine increases CD14 + CD16+ monocyte migration and adhesion in the context of substance abuse and HIV neuropathogenesis. PLoS One 10(2):e0117450. https://doi.org/10.1371/journal.pone.0117450CrossRefPubMedPubMedCentral

51.

Davis BK, Wen H, Ting JP (2011) The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol 29:707–735. https://doi.org/10.1146/annurev-immunol-031210-101405CrossRefPubMedPubMedCentral

52.

Martinon F, Mayor A, Tschopp J (2009) The inflammasomes: guardians of the body. Annu Rev Immunol 27:229–265. https://doi.org/10.1146/annurev.immunol.021908.132715CrossRefPubMed

53.

Bauernfeind F, Niepmann S, Knolle PA, Hornung V (2016) Aging-associated TNF production primes inflammasome activation and NLRP3-related metabolic disturbances. J Immunol 197(7):2900–2908. https://doi.org/10.4049/jimmunol.1501336CrossRefPubMed

54.

Lamkanfi M, Dixit VM (2012) Inflammasomes and their roles in health and disease. Annu Rev Cell Dev Biol 28:137–161. https://doi.org/10.1146/annurev-cellbio-101011-155745CrossRefPubMed

55.

Tschopp J, Schroder K (2010) NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol 10(3):210–215. https://doi.org/10.1038/nri2725CrossRefPubMed

56.

Shimojo G, Joseph B, Shah R, Consolim-Colombo FM, De Angelis K, Ulloa L (2019) Exercise activates vagal induction of dopamine and attenuates systemic inflammation. Brain Behav Immun 75:181–191. https://doi.org/10.1016/j.bbi.2018.10.005CrossRefPubMed

57.

Feketeova E, Li Z, Joseph B, Shah R, Spolarics Z, Ulloa L (2018) Dopaminergic control of inflammation and glycemia in sepsis and diabetes. Front Immunol 9:943. https://doi.org/10.3389/fimmu.2018.00943CrossRefPubMedPubMedCentral

58.

Kohut ML, Davis JM, Jackson DA, Colbert LH, Strasner A, Essig DA, Pate RR, Ghaffar A, Mayer EP (1998) The role of stress hormones in exercise-induced suppression of alveolar macrophage antiviral function. J Neuroimmunol 81(1-2):193–200. https://doi.org/10.1016/s0165-5728(97)00179-3CrossRefPubMed

59.

van der Poll T, Coyle SM, Barbosa K, Braxton CC, Lowry SF (1996) Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia. J Clin Invest 97(3):713–719. https://doi.org/10.1172/JCI118469CrossRefPubMedPubMedCentral

60.

Agac D, Estrada LD, Maples R, Hooper LV, Farrar JD (2018) The beta2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion. Brain Behav Immun 74:176–185. https://doi.org/10.1016/j.bbi.2018.09.004CrossRefPubMedPubMedCentral

61.

Maisel AS, Knowlton KU, Fowler P, Rearden A, Ziegler MG, Motulsky HJ, Insel PA, Michel MC (1990) Adrenergic control of circulating lymphocyte subpopulations. Effects of congestive heart failure, dynamic exercise, and terbutaline treatment. J Clin Invest 85(2):462–467. https://doi.org/10.1172/JCI114460CrossRefPubMedPubMedCentral

62.

Itoh CE, Kizaki T, Hitomi Y, Hanawa T, Kamiya S, Ookawara T, Suzuki K, Izawa T, Saitoh D, Haga S, Ohno H (2004) Down-regulation of beta2-adrenergic receptor expression by exercise training increases IL-12 production by macrophages following LPS stimulation. Biochem Biophys Res Commun 322(3):979–984. https://doi.org/10.1016/j.bbrc.2004.08.050CrossRefPubMed

63.

Coppo M, Bandinelli M, Chiostri M, Poggesi L, Boddi M (2017) Persistent and selective upregulation of renin-angiotensin system in circulating T lymphocytes in unstable angina. J Renin-Angiotensin-Aldosterone Syst 18(1):1470320317698849. https://doi.org/10.1177/1470320317698849CrossRefPubMedPubMedCentral

64.

Ruiz-Ortega M, Bustos C, Hernandez-Presa MA, Lorenzo O, Plaza JJ, Egido J (1998) Angiotensin II participates in mononuclear cell recruitment in experimental immune complex nephritis through nuclear factor-kappa B activation and monocyte chemoattractant protein-1 synthesis. J Immunol 161(1):430–439PubMed

65.

Silva-Filho JL, Souza MC, Henriques MG, Morrot A, Savino W, Caruso-Neves C, Pinheiro AA (2015) Renin-angiotensin system contributes to naive T-cell migration in vivo. Arch Biochem Biophys 573:1–13. https://doi.org/10.1016/j.abb.2015.02.035CrossRefPubMed

66.

Hoch NE, Guzik TJ, Chen W, Deans T, Maalouf SA, Gratze P, Weyand C, Harrison DG (2009) Regulation of T-cell function by endogenously produced angiotensin II. Am J Phys Regul Integr Comp Phys 296(2):R208–R216. https://doi.org/10.1152/ajpregu.90521.2008CrossRef

67.

Carey RM (2013) The intrarenal renin-angiotensin and dopaminergic systems: control of renal sodium excretion and blood pressure. Hypertension 61(3):673–680. https://doi.org/10.1161/HYPERTENSIONAHA.111.00241CrossRefPubMed

68.

Matsuyama T, Ohashi N, Ishigaki S, Isobe S, Tsuji N, Fujikura T, Tsuji T, Kato A, Miyajima H, Yasuda H (2018) The relationship between the intrarenal dopamine system and intrarenal renin-angiotensin system depending on the renal function. Intern Med 57(22):3241–3247. https://doi.org/10.2169/internalmedicine.0994-18CrossRefPubMedPubMedCentral

69.

Rukavina Mikusic NL, Kouyoumdzian NM, Uceda A, Del Mauro JS, Pandolfo M, Gironacci MM, Puyo AM, Toblli JE, Fernandez BE, Choi MR (2018) Losartan prevents the imbalance between renal dopaminergic and renin angiotensin systems induced by fructose overload. l-Dopa/dopamine index as new potential biomarker of renal dysfunction. Metabolism 85:271–285. https://doi.org/10.1016/j.metabol.2018.04.010CrossRefPubMed

70.

Yang S, Yao B, Zhou Y, Yin H, Zhang MZ, Harris RC (2012) Intrarenal dopamine modulates progressive angiotensin II-mediated renal injury. Am J Physiol Ren Physiol 302(6):F742–F749. https://doi.org/10.1152/ajprenal.00583.2011CrossRef

71.

Khan F, Spicarova Z, Zelenin S, Holtback U, Scott L, Aperia A (2008) Negative reciprocity between angiotensin II type 1 and dopamine D1 receptors in rat renal proximal tubule cells. Am J Physiol Ren Physiol 295(4):F1110–F1116. https://doi.org/10.1152/ajprenal.90336.2008CrossRef

72.

Ihara S, Hirata Y, Koike K (2017) TGF-beta in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota. J Gastroenterol 52(7):777–787. https://doi.org/10.1007/s00535-017-1350-1CrossRefPubMed

73.

Abraham BP, Ahmed T, Ali T (2017) Inflammatory bowel disease: pathophysiology and current therapeutic approaches. Handb Exp Pharmacol 239:115–146. https://doi.org/10.1007/164_2016_122CrossRefPubMed

74.

Azimi T, Nasiri MJ, Chirani AS, Pouriran R, Dabiri H (2018) The role of bacteria in the inflammatory bowel disease development: a narrative review. APMIS 126(4):275–283. https://doi.org/10.1111/apm.12814CrossRefPubMed

75.

Campos-Acuna J, Elgueta D, Pacheco R (2019) T-cell-driven inflammation as a mediator of the gut-brain axis involved in Parkinson’s disease. Front Immunol 10:239. https://doi.org/10.3389/fimmu.2019.00239CrossRefPubMedPubMedCentral

76.

Wu W, Sun M, Zhang HP, Chen T, Wu R, Liu C, Yang G, Geng XR, Feng BS, Liu Z, Liu Z, Yang PC (2014) Prolactin mediates psychological stress-induced dysfunction of regulatory T cells to facilitate intestinal inflammation. Gut 63(12):1883–1892. https://doi.org/10.1136/gutjnl-2013-306083CrossRefPubMed

77.

Tolstanova G, Deng X, Ahluwalia A, Paunovic B, Prysiazhniuk A, Ostapchenko L, Tarnawski A, Sandor Z, Szabo S (2015) Role of dopamine and D2 dopamine receptor in the pathogenesis of inflammatory bowel disease. Dig Dis Sci 60(10):2963–2975. https://doi.org/10.1007/s10620-015-3698-5CrossRefPubMed

78.

Shi Y, Liu T, He L, Dougherty U, Chen L, Adhikari S, Alpert L, Zhou G, Liu W, Wang J, Deb DK, Hart J, Liu SQ, Kwon J, Pekow J, Rubin DT, Zhao Q, Bissonnette M, Li YC (2016) Activation of the renin-angiotensin system promotes colitis development. Sci Rep 6:27552. https://doi.org/10.1038/srep27552CrossRefPubMedPubMedCentral

79.

Garrido-Gil P, Dominguez-Meijide A, Moratalla R, Guerra MJ, Labandeira-Garcia JL (2018) Aging-related dysregulation in enteric dopamine and angiotensin system interactions: implications for gastrointestinal dysfunction in the elderly. Oncotarget 9(13):10834–10846. https://doi.org/10.18632/oncotarget.24330CrossRefPubMedPubMedCentral

80.

Yang G, Gray TS, Sigmund CD, Cassell MD (1999) The angiotensinogen gene is expressed in both astrocytes and neurons in murine central nervous system. Brain Res 817(1-2):123–131. https://doi.org/10.1016/s0006-8993(98)01236-0CrossRefPubMed

81.

Stornetta RL, Hawelu-Johnson CL, Guyenet PG, Lynch KR (1988) Astrocytes synthesize angiotensinogen in brain. Science 242(4884):1444–1446. https://doi.org/10.1126/science.3201232CrossRefPubMed

82.

Cuadra AE, Shan Z, Sumners C, Raizada MK (2010) A current view of brain renin-angiotensin system: Is the (pro)renin receptor the missing link? Pharmacol Ther 125(1):27–38. https://doi.org/10.1016/j.pharmthera.2009.07.007CrossRefPubMed

83.

Dominguez-Meijide A, Rodriguez-Perez AI, Diaz-Ruiz C, Guerra MJ, Labandeira-Garcia JL (2017) Dopamine modulates astroglial and microglial activity via glial renin-angiotensin system in cultures. Brain Behav Immun 62:277–290. https://doi.org/10.1016/j.bbi.2017.02.013CrossRefPubMed

84.

Gonzalez H, Pacheco R (2014) T-cell-mediated regulation of neuroinflammation involved in neurodegenerative diseases. J Neuroinflammation 11(1):201. https://doi.org/10.1186/s12974-014-0201-8CrossRefPubMedPubMedCentral

85.

Munoz A, Garrido-Gil P, Dominguez-Meijide A, Labandeira-Garcia JL (2014) Angiotensin type 1 receptor blockage reduces l-dopa-induced dyskinesia in the 6-OHDA model of Parkinson’s disease. Involvement of vascular endothelial growth factor and interleukin-1beta. Exp Neurol 261:720–732. https://doi.org/10.1016/j.expneurol.2014.08.019CrossRefPubMed

86.

Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24(2):197–211. https://doi.org/10.1016/s0197-4580(02)00065-9CrossRefPubMed

87.

Braak H, Rub U, Gai WP, Del Tredici K (2003) Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 110(5):517–536. https://doi.org/10.1007/s00702-002-0808-2CrossRefPubMed

88.

Garrido-Gil P, Rodriguez-Perez AI, Dominguez-Meijide A, Guerra MJ, Labandeira-Garcia JL (2018) Bidirectional neural interaction between central dopaminergic and gut lesions in Parkinson’s disease models. Mol Neurobiol 55:7297–7316. https://doi.org/10.1007/s12035-018-0937-8CrossRefPubMed

89.

Rodriguez-Pallares J, Rey P, Parga JA, Munoz A, Guerra MJ, Labandeira-Garcia JL (2008) Brain angiotensin enhances dopaminergic cell death via microglial activation and NADPH-derived ROS. Neurobiol Dis 31(1):58–73. https://doi.org/10.1016/j.nbd.2008.03.003CrossRefPubMed

90.

Joglar B, Rodriguez-Pallares J, Rodriguez-Perez AI, Rey P, Guerra MJ, Labandeira-Garcia JL (2009) The inflammatory response in the MPTP model of Parkinson’s disease is mediated by brain angiotensin: relevance to progression of the disease. J Neurochem 109(2):656–669. https://doi.org/10.1111/j.1471-4159.2009.05999.xCrossRefPubMed

91.

Labandeira-Garcia JL, Garrido-Gil P, Rodriguez-Pallares J, Valenzuela R, Borrajo A, Rodriguez-Perez AI (2014) Brain renin-angiotensin system and dopaminergic cell vulnerability. Front Neuroanat 8:67. https://doi.org/10.3389/fnana.2014.00067CrossRefPubMedPubMedCentral

92.

Abeliovich A, Gitler AD (2016) Defects in trafficking bridge Parkinson’s disease pathology and genetics. Nature 539(7628):207–216. https://doi.org/10.1038/nature20414CrossRefPubMed

93.

Montoya A, Elgueta D, Campos J, Chovar O, Falcon P, Matus S, Alfaro I, Bono MR, Pacheco R (2019) Dopamine receptor D3 signalling in astrocytes promotes neuroinflammation. J Neuroinflammation 16(1):258. https://doi.org/10.1186/s12974-019-1652-8CrossRefPubMedPubMedCentral

94.

Shao W, Zhang SZ, Tang M, Zhang XH, Zhou Z, Yin YQ, Zhou QB, Huang YY, Liu YJ, Wawrousek E, Chen T, Li SB, Xu M, Zhou JN, Hu G, Zhou JW (2013) Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alphaB-crystallin. Nature 494(7435):90–94. https://doi.org/10.1038/nature11748CrossRefPubMed

95.

Fletcher JM, Lalor SJ, Sweeney CM, Tubridy N, Mills KH (2010) T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol 162(1):1–11. https://doi.org/10.1111/j.1365-2249.2010.04143.xCrossRefPubMedPubMedCentral

96.

Haider L, Fischer MT, Frischer JM, Bauer J, Hoftberger R, Botond G, Esterbauer H, Binder CJ, Witztum JL, Lassmann H (2011) Oxidative damage in multiple sclerosis lesions. Brain J Neurol 134(Pt 7):1914–1924. https://doi.org/10.1093/brain/awr128CrossRef

97.

Smith KJ (2011) Newly lesioned tissue in multiple sclerosis--a role for oxidative damage? Brain J Neurol 134(Pt 7):1877–1881. https://doi.org/10.1093/brain/awr144CrossRef

98.

Kawajiri M, Mogi M, Higaki N, Matsuoka T, Ohyagi Y, Tsukuda K, Kohara K, Horiuchi M, Miki T, Kira JI (2009) Angiotensin-converting enzyme (ACE) and ACE2 levels in the cerebrospinal fluid of patients with multiple sclerosis. Mult Scler 15(2):262–265. https://doi.org/10.1177/1352458508097923CrossRefPubMed

99.

Platten M, Youssef S, Hur EM, Ho PP, Han MH, Lanz TV, Phillips LK, Goldstein MJ, Bhat R, Raine CS, Sobel RA, Steinman L (2009) Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity. Proc Natl Acad Sci U S A 106(35):14948–14953. https://doi.org/10.1073/pnas.0903958106CrossRefPubMedPubMedCentral

100.

Kaasinen V, Joutsa J, Rissanen E, Airas L, Soilu-Hanninen M, Noponen T (2019) Progressive dopaminergic defect in a patient with primary progressive multiple sclerosis. Mult Scler Relat Disord 36:101385. https://doi.org/10.1016/j.msard.2019.101385CrossRefPubMed

101.

Lund BT, Stone R, Levy AM, Lee S, Amundson E, Kashani N, Rodgers KE, Kelland EE (2019) Reduced disease severity following therapeutic treatment with angiotensin 1-7 in a mouse model of multiple sclerosis. Neurobiol Dis 127:87–100. https://doi.org/10.1016/j.nbd.2019.02.018CrossRefPubMed

102.

Hammer A, Yang G, Friedrich J, Kovacs A, Lee DH, Grave K, Jorg S, Alenina N, Grosch J, Winkler J, Gold R, Bader M, Manzel A, Rump LC, Muller DN, Linker RA, Stegbauer J (2016) Role of the receptor Mas in macrophage-mediated inflammation in vivo. Proc Natl Acad Sci U S A 113(49):14109–14114. https://doi.org/10.1073/pnas.1612668113CrossRefPubMedPubMedCentral

103.

Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI (2005) Host-bacterial mutualism in the human intestine. Science 307(5717):1915–1920. https://doi.org/10.1126/science.1104816CrossRefPubMed

104.

Pacheco R (2019) Cross-talk between T-cells and gut-microbiota in neurodegenerative disorders. Neural Regen Res 14(12):2091–2092. https://doi.org/10.4103/1673-5374.262582CrossRefPubMedPubMedCentral

105.

Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Burmann J, Fassbender K, Schwiertz A, Schafer KH (2016) Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord 32:66–72. https://doi.org/10.1016/j.parkreldis.2016.08.019CrossRefPubMed

106.

Marino E, Richards JL, McLeod KH, Stanley D, Yap YA, Knight J, McKenzie C, Kranich J, Oliveira AC, Rossello FJ, Krishnamurthy B, Nefzger CM, Macia L, Thorburn A, Baxter AG, Morahan G, Wong LH, Polo JM, Moore RJ, Lockett TJ, Clarke JM, Topping DL, Harrison LC, Mackay CR (2017) Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol 18(5):552–562. https://doi.org/10.1038/ni.3713CrossRefPubMed

107.

Haase S, Haghikia A, Wilck N, Muller DN, Linker RA (2018) Impacts of microbiome metabolites on immune regulation and autoimmunity. Immunology 154(2):230–238. https://doi.org/10.1111/imm.12933CrossRefPubMedPubMedCentral

108.

Hui W, Yu D, Cao Z, Zhao X (2019) Butyrate inhibit collagen-induced arthritis via Treg/IL-10/Th17 axis. Int Immunopharmacol 68:226–233. https://doi.org/10.1016/j.intimp.2019.01.018CrossRefPubMed

109.

Macfarlane S, Macfarlane GT (2003) Regulation of short-chain fatty acid production. Proc Nutr Soc 62(1):67–72. https://doi.org/10.1079/PNS2002207CrossRefPubMed

110.

Hoyles L, Snelling T, Umlai UK, Nicholson JK, Carding SR, Glen RC, McArthur S (2018) Microbiome-host systems interactions: protective effects of propionate upon the blood-brain barrier. Microbiome 6(1):55. https://doi.org/10.1186/s40168-018-0439-yCrossRefPubMedPubMedCentral

111.

Morris G, Berk M, Carvalho A, Caso JR, Sanz Y, Walder K, Maes M (2017) The role of the microbial metabolites including tryptophan catabolites and short chain fatty acids in the pathophysiology of immune-inflammatory and neuroimmune disease. Mol Neurobiol 54(6):4432–4451. https://doi.org/10.1007/s12035-016-0004-2CrossRefPubMed

112.

Suarez-Zamorano N, Fabbiano S, Chevalier C, Stojanovic O, Colin DJ, Stevanovic A, Veyrat-Durebex C, Tarallo V, Rigo D, Germain S, Ilievska M, Montet X, Seimbille Y, Hapfelmeier S, Trajkovski M (2015) Microbiota depletion promotes browning of white adipose tissue and reduces obesity. Nat Med 21(12):1497–1501. https://doi.org/10.1038/nm.3994CrossRefPubMedPubMedCentral

113.

Wang L, Zhu Q, Lu A, Liu X, Zhang L, Xu C, Liu X, Li H, Yang T (2017) Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin-angiotensin system. J Hypertens 35(9):1899–1908. https://doi.org/10.1097/HJH.0000000000001378CrossRefPubMed

114.

Dave LA, Hayes M, Montoya CA, Rutherfurd SM, Moughan PJ (2016) Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides. Peptides 76:30–44. https://doi.org/10.1016/j.peptides.2015.11.003CrossRefPubMed

115.

Asano Y, Hiramoto T, Nishino R, Aiba Y, Kimura T, Yoshihara K, Koga Y, Sudo N (2012) Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Physiol Gastrointest Liver Physiol 303(11):G1288–G1295. https://doi.org/10.1152/ajpgi.00341.2012CrossRefPubMed

116.

Diaz Heijtz R, Wang S, Anuar F, Qian Y, Bjorkholm B, Samuelsson A, Hibberd ML, Forssberg H, Pettersson S (2011) Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A 108(7):3047–3052. https://doi.org/10.1073/pnas.1010529108CrossRefPubMed

117.

Koronyo-Hamaoui M, Sheyn J, Hayden EY, Li S, Fuchs DT, Regis GC, Lopes DHJ, Black KL, Bernstein KE, Teplow DB, Fuchs S, Koronyo Y, Rentsendorj A (2020) Peripherally derived angiotensin converting enzyme-enhanced macrophages alleviate Alzheimer-related disease. Brain J Neurol 143(1):336–358. https://doi.org/10.1093/brain/awz364CrossRef

118.

Ongali B, Nicolakakis N, Tong XK, Lecrux C, Imboden H, Hamel E (2018) Transforming growth factor-beta1 induces cerebrovascular dysfunction and astrogliosis through angiotensin II type 1 receptor-mediated signaling pathways. Can J Physiol Pharmacol 96(5):527–534. https://doi.org/10.1139/cjpp-2017-0640CrossRefPubMed

119.

Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, Shi H, Thangaraju M, Prasad PD, Manicassamy S, Munn DH, Lee JR, Offermanns S, Ganapathy V (2014) Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40(1):128–139. https://doi.org/10.1016/j.immuni.2013.12.007CrossRefPubMedPubMedCentral

120.

Gong X, Hu H, Qiao Y, Xu P, Yang M, Dang R, Han W, Guo Y, Chen D, Jiang P (2019) The involvement of renin-angiotensin system in lipopolysaccharide-induced behavioral changes, neuroinflammation, and disturbed insulin signaling. Front Pharmacol 10:318. https://doi.org/10.3389/fphar.2019.00318CrossRefPubMedPubMedCentral

121.

Drews HJ, Yenkoyan K, Lourhmati A, Buadze M, Kabisch D, Verleysdonk S, Petschak S, Beer-Hammer S, Davtyan T, Frey WH 2nd, Gleiter CH, Schwab M, Danielyan L (2019) Intranasal losartan decreases perivascular beta amyloid, inflammation, and the decline of neurogenesis in hypertensive rats. Neurotherapeutics 16(3):725–740. https://doi.org/10.1007/s13311-019-00723-6CrossRefPubMedPubMedCentral

122.

Trigiani LJ, Royea J, Lacalle-Aurioles M, Tong XK, Hamel E (2018) pleiotropic benefits of the angiotensin receptor blocker candesartan in a mouse model of Alzheimer disease. Hypertension 72(5):1217–1226. https://doi.org/10.1161/HYPERTENSIONAHA.118.11775CrossRefPubMed

123.

Rodriguez-Perez AI, Sucunza D, Pedrosa MA, Garrido-Gil P, Kulisevsky J, Lanciego JL, Labandeira-Garcia JL (2018) Angiotensin type 1 receptor antagonists protect against alpha-synuclein-induced neuroinflammation and dopaminergic neuron death. Neurotherapeutics 15(4):1063–1081. https://doi.org/10.1007/s13311-018-0646-zCrossRefPubMedPubMedCentral

124.

Salmani H, Hosseini M, Beheshti F, Baghcheghi Y, Sadeghnia HR, Soukhtanloo M, Shafei MN, Khazaei M (2018) Angiotensin receptor blocker, losartan ameliorates neuroinflammation and behavioral consequences of lipopolysaccharide injection. Life Sci 203:161–170. https://doi.org/10.1016/j.lfs.2018.04.033CrossRefPubMed

125.

Khallaf WAI, Messiha BAS, Abo-Youssef AMH, El-Sayed NS (2017) Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation, and amyloidogenesis: possible role of brain-derived neurotrophic factor. Can J Physiol Pharmacol 95(7):850–860. https://doi.org/10.1139/cjpp-2017-0042CrossRefPubMed

126.

Ali MR, Abo-Youssef AM, Messiha BA, Khattab MM (2016) Tempol and perindopril protect against lipopolysaccharide-induced cognition impairment and amyloidogenesis by modulating brain-derived neurotropic factor, neuroinflammation and oxido-nitrosative stress. Naunyn Schmiedeberg's Arch Pharmacol 389(6):637–656. https://doi.org/10.1007/s00210-016-1234-6CrossRef

127.

Garrido-Gil P, Joglar B, Rodriguez-Perez AI, Guerra MJ, Labandeira-Garcia JL (2012) Involvement of PPAR-gamma in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease. J Neuroinflammation 9:38. https://doi.org/10.1186/1742-2094-9-38CrossRefPubMedPubMedCentral

128.

Dominguez-Meijide A, Villar-Cheda B, Garrido-Gil P, Sierrra-Paredes G, Guerra MJ, Labandeira-Garcia JL (2014) Effect of chronic treatment with angiotensin type 1 receptor antagonists on striatal dopamine levels in normal rats and in a rat model of Parkinson's disease treated with L-DOPA. Neuropharmacology 76(Pt A):156–168. https://doi.org/10.1016/j.neuropharm.2013.07.016CrossRefPubMed

129.

Sonsalla PK, Coleman C, Wong LY, Harris SL, Richardson JR, Gadad BS, Li W, German DC (2013) The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism. Exp Neurol 250:376–383. https://doi.org/10.1016/j.expneurol.2013.10.014CrossRefPubMedPubMedCentral

130.

Borrajo A, Rodriguez-Perez AI, Diaz-Ruiz C, Guerra MJ, Labandeira-Garcia JL (2014) Microglial TNF-alpha mediates enhancement of dopaminergic degeneration by brain angiotensin. Glia 62(1):145–157. https://doi.org/10.1002/glia.22595CrossRefPubMed

131.

Guo X, Namekata K, Kimura A, Harada C, Harada T (2017) The renin-angiotensin system regulates neurodegeneration in a mouse model of optic neuritis. Am J Pathol 187(12):2876–2885. https://doi.org/10.1016/j.ajpath.2017.08.012CrossRefPubMed

132.

Mori K, Yoshida K, Tani J, Nakagawa Y, Hoshikawa S, Ozaki H, Ito S (2008) Effects of angiotensin II blockade on the development of autoimmune thyroiditis in nonobese diabetic mice. Clin Immunol 126(1):97–103. https://doi.org/10.1016/j.clim.2007.08.018CrossRefPubMed

133.

Uzawa A, Mori M, Taniguchi J, Kuwabara S (2014) Modulation of the kallikrein/kinin system by the angiotensin-converting enzyme inhibitor alleviates experimental autoimmune encephalomyelitis. Clin Exp Immunol 178(2):245–252. https://doi.org/10.1111/cei.12413CrossRefPubMedPubMedCentral

134.

Okunuki Y, Usui Y, Nagai N, Kezuka T, Ishida S, Takeuchi M, Goto H (2009) Suppression of experimental autoimmune uveitis by angiotensin II type 1 receptor blocker telmisartan. Invest Ophthalmol Vis Sci 50(5):2255–2261. https://doi.org/10.1167/iovs.08-2649CrossRefPubMed

135.

Miyazaki A, Kitaichi N, Ohgami K, Iwata D, Jin XH, Iwabuchi K, Morohashi T, Ohno S, Onoe K (2008) Anti-inflammatory effect of angiotensin type 1 receptor antagonist on endotoxin-induced uveitis in rats. Graefes Arch Clin Exp Ophthalmol 246(5):747–757. https://doi.org/10.1007/s00417-007-0730-2CrossRefPubMed

136.

Wang T, Nowrangi D, Yu L, Lu T, Tang J, Han B, Ding Y, Fu F, Zhang JH (2018) Activation of dopamine D1 receptor decreased NLRP3-mediated inflammation in intracerebral hemorrhage mice. J Neuroinflammation 15(1):2. https://doi.org/10.1186/s12974-017-1039-7CrossRefPubMedPubMedCentral

137.

Zhu J, Hu Z, Han X, Wang D, Jiang Q, Ding J, Xiao M, Wang C, Lu M, Hu G (2018) Dopamine D2 receptor restricts astrocytic NLRP3 inflammasome activation via enhancing the interaction of beta-arrestin2 and NLRP3. Cell Death Differ 25(11):2037–2049. https://doi.org/10.1038/s41418-018-0127-2CrossRefPubMedPubMedCentral

138.

Lieberknecht V, Junqueira SC, Cunha MP, Barbosa TA, de Souza LF, Coelho IS, Santos AR, Rodrigues AL, Dafre AL, Dutra RC (2017) Pramipexole, a dopamine D2/D3 receptor-preferring agonist, prevents experimental autoimmune encephalomyelitis development in mice. Mol Neurobiol 54(2):1033–1045. https://doi.org/10.1007/s12035-016-9717-5CrossRefPubMed

139.

Kawano M, Takagi R, Kaneko A, Matsushita S (2015) Berberine is a dopamine D1- and D2-like receptor antagonist and ameliorates experimentally induced colitis by suppressing innate and adaptive immune responses. J Neuroimmunol 289:43–55. https://doi.org/10.1016/j.jneuroim.2015.10.001CrossRefPubMed

140.

Du RH, Zhou Y, Xia ML, Lu M, Ding JH, Hu G (2018) alpha-Synuclein disrupts the anti-inflammatory role of Drd2 via interfering beta-arrestin2-TAB1 interaction in astrocytes. J Neuroinflammation 15(1):258. https://doi.org/10.1186/s12974-018-1302-6CrossRefPubMedPubMedCentral

141.

Sadeghi H, Parishani M, Akbartabar Touri M, Ghavamzadeh M, Jafari Barmak M, Zarezade V, Delaviz H, Sadeghi H (2017) Pramipexole reduces inflammation in the experimental animal models of inflammation. Immunopharmacol Immunotoxicol 39(2):80–86. https://doi.org/10.1080/08923973.2017.1284230CrossRefPubMed

142.

Melnikov M, Belousova O, Murugin V, Pashenkov capital Em C, Boysmall ka CoCA (2016) The role of dopamine in modulation of Th-17 immune response in multiple sclerosis. J Neuroimmunol 292:97-101. doi:https://doi.org/10.1016/j.jneuroim.2016.01.020

143.

Nakano K, Yamaoka K, Hanami K, Saito K, Sasaguri Y, Yanagihara N, Tanaka S, Katsuki I, Matsushita S, Tanaka Y (2011) Dopamine induces IL-6-dependent IL-17 production via D1-like receptor on CD4 naive T cells and D1-like receptor antagonist SCH-23390 inhibits cartilage destruction in a human rheumatoid arthritis/SCID mouse chimera model. J Immunol 186(6):3745–3752. https://doi.org/10.4049/jimmunol.1002475CrossRefPubMed

144.

Nakano K, Higashi T, Hashimoto K, Takagi R, Tanaka Y, Matsushita S (2008) Antagonizing dopamine D1-like receptor inhibits Th17 cell differentiation: preventive and therapeutic effects on experimental autoimmune encephalomyelitis. Biochem Biophys Res Commun 373(2):286–291CrossRefPubMed

Title: Involvement of dopaminergic signaling in the cross talk between the renin-angiotensin system and inflammation
Authors: Javier Campos
Rodrigo Pacheco
Publication date: 01-12-2020
Publisher: Springer Berlin Heidelberg
Keywords: Chronic Inflammatory Bowel Disease
Parkinson's Disease
Candesartan
Published in: Seminars in Immunopathology / Issue 6/2020
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-020-00819-8

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2020

Stress reduction strategies in breast cancer: review of pharmacologic and non-pharmacologic based strategies

Interactions among microbes, the immune system, and the circadian clock

Adrenergic regulation of immune cell function and inflammation

Neuro-immune interactions

Control of immunity by glucocorticoids in health and disease

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage