Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

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.
ADVANCED SEARCH
Log in
Top
Journal of Inflammation
Published in: Journal of Inflammation 1/2015

Open Access 01-12-2015 | Review

Coupled cell networks are target cells of inflammation, which can spread between different body organs and develop into systemic chronic inflammation

Authors: Elisabeth Hansson, Eva Skiöldebrand

Published in: Journal of Inflammation | Issue 1/2015

Login to get access

Abstract

Several organs in the body comprise cells coupled into networks. These cells have in common that they are excitable but do not express action potentials. Furthermore, they are equipped with Ca2+ signaling systems, which can be intercellular and/or extracellular. The transport of small molecules between the cells occurs through gap junctions comprising connexin 43. Examples of cells coupled into networks include astrocytes, keratinocytes, chondrocytes, synovial fibroblasts, osteoblasts, connective tissue cells, cardiac and corneal fibroblasts, myofibroblasts, hepatocytes, and different types of glandular cells. These cells are targets for inflammation, which can be initiated after injury or in disease. If the inflammation reaches the CNS, it develops into neuroinflammation and can be of importance in the development of systemic chronic inflammation, which can manifest as pain and result in changes in the expression and structure of cellular components. Biochemical parameters of importance for cellular functions are described in this review.
Literature
1.
Machelska H. Dual peripheral actions of immune cells in neuropathic pain. Arch Immunol Ther Exp (Warsz). 2011;59:11–24.
2.
Huang E, Wells CA. The ground state of innate immune responsiveness is determined at the interface of genetic, epigenetic, and environmental influences. J Immunol. 2014;193:13–9.PubMed
3.
Huber JD, Witt KA, Hom S, Egleton RD, Mark KS, Davis TP. Inflammatory pain alters blood–brain barrier permeability and tight junctional protein expression. Am J Physiol Heart Circ Physiol. 2001;280:H1241–1248.PubMed
4.
Sharma HS, Johanson CE. Blood-cerebrospinal fluid barrier in hyperthermia. Prog Brain Res. 2007;162:459–78.PubMed
5.
Fuggle NR, Howe FA, Allen RL, Sofat N. New insights into the impact of neuro-inflammation in rheumatoid arthritis. Front Neurosci. 2014;8:357.PubMedCentralPubMed
6.
Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood–brain barrier. Nat Rev Neurosci. 2006;7:41–53.PubMed
7.
Saade NE, Jabbur SJ. Nociceptive behavior in animal models for peripheral neuropathy: spinal and supraspinal mechanisms. Prog Neurobiol. 2008;86:22–47.PubMed
8.
McMahon SB, Malcangio M. Current challenges in glia-pain biology. Neuron. 2009;64:46–54.PubMed
9.
Vallejo R, Tilley DM, Vogel L, Benyamin R. The role of glia and the immune system in the development and maintenance of neuropathic pain. Pain Pract. 2010;10:167–84.PubMed
10.
11.
Jansson D, Rustenhoven J, Feng S, Hurley D, Oldfield RL, Bergin PS, et al. A role for human brain pericytes in neuroinflammation. J Neuroinflammation. 2014;11:104.PubMedCentralPubMed
12.
LeBleu VS, Taduri G, O'Connell J, Teng Y, Cooke VG, Woda C, et al. Origin and function of myofibroblasts in kidney fibrosis. Nat Med. 2013;19:1047–53.PubMedCentralPubMed
13.
Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007;10:1361–8.PubMed
14.
15.
DeLeo JA, Tanga FY, Tawfik VL. Neuroimmune activation and neuroinflammation in chronic pain and opioid tolerance/hyperalgesia. Neuroscientist. 2004;10:40–52.PubMed
16.
17.
Tenorio G, Kulkarni A, Kerr BJ. Resident glial cell activation in response to perispinal inflammation leads to acute changes in nociceptive sensitivity: implications for the generation of neuropathic pain. Pain. 2013;154:71–81.PubMed
18.
Koltzenburg M, Wall PD, McMahon SB. Does the right side know what the left is doing? Trends Neurosci. 1999;22:122–7.PubMed
19.
Blomstrand F, Khatibi S, Muyderman H, Hansson E, Olsson T, Ronnback L. 5-Hydroxytryptamine and glutamate modulate velocity and extent of intercellular calcium signalling in hippocampal astroglial cells in primary cultures. Neuroscience. 1999;88:1241–53.PubMed
20.
Berridge MJ, Bootman MD, Lipp P. Calcium--a life and death signal. Nature. 1998;395:645–8.PubMed
21.
Zorec R, Araque A, Carmignoto G, Haydon PG, Verkhratsky A, Parpura V. Astroglial excitability and gliotransmission: an appraisal of Ca2+ as a signalling route. ASN Neuro 2012; 4. doi:10.​1042/​AN20110061.
22.
Head BP, Patel HH, Insel PA. Interaction of membrane/lipid rafts with the cytoskeleton: impact on signaling and function: membrane/lipid rafts, mediators of cytoskeletal arrangement and cell signaling. Biochim Biophys Acta. 1838;2014:532–45.
23.
Giaume C, McCarthy KD. Control of gap-junctional communication in astrocytic networks. Trends Neurosci. 1996;19:319–25.PubMed
24.
Bennett MV, Garre JM, Orellana JA, Bukauskas FF, Nedergaard M, Saez JC. Connexin and pannexin hemichannels in inflammatory responses of glia and neurons. Brain Res. 2012;1487:3–15.PubMedCentralPubMed
25.
Chen MJ, Kress B, Han X, Moll K, Peng W, Ji RR, et al. Astrocytic CX43 hemichannels and gap junctions play a crucial role in development of chronic neuropathic pain following spinal cord injury. Glia. 2012;60:1660–70.PubMedCentralPubMed
26.
Oda T, Iwasa M, Aihara T, Maeda Y, Narita A. The nature of the globular- to fibrous-actin transition. Nature. 2009;457:441–5.PubMed
27.
Kimelberg HK, Macvicar BA, Sontheimer H. Anion channels in astrocytes: biophysics, pharmacology, and function. Glia. 2006;54:747–57.PubMedCentralPubMed
28.
29.
30.
Cornell-Bell AH, Finkbeiner SM, Cooper MS, Smith SJ. Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science. 1990;247:470–3.PubMed
31.
Lencesova L, O'Neill A, Resneck WG, Bloch RJ, Blaustein MP. Plasma membrane-cytoskeleton-endoplasmic reticulum complexes in neurons and astrocytes. J Biol Chem. 2004;279:2885–93.PubMed
32.
Liu X, Spicarova Z, Rydholm S, Li J, Brismar H, Aperia A. Ankyrin B modulates the function of Na, K-ATPase/inositol 1,4,5-trisphosphate receptor signaling microdomain. J Biol Chem. 2008;283:11461–8.PubMed
33.
Hansson E, Ronnback L. Glial neuronal signaling in the central nervous system. FASEB J. 2003;17:341–8.PubMed
34.
Hansson E. Could chronic pain and spread of pain sensation be induced and maintained by glial activation? Acta Physiol (Oxf). 2006;187:321–7.
35.
Delbro D, Westerlund A, Bjorklund U, Hansson E. In inflammatory reactive astrocytes co-cultured with brain endothelial cells nicotine-evoked Ca(2+) transients are attenuated due to interleukin-1beta release and rearrangement of actin filaments. Neuroscience. 2009;159:770–9.PubMed
36.
Cotrina ML, Lin JH, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, et al. Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci U S A. 1998;95:15735–40.PubMedCentralPubMed
37.
Edwards JR, Gibson WG. A model for Ca2+ waves in networks of glial cells incorporating both intercellular and extracellular communication pathways. J Theor Biol. 2010;263:45–58.PubMed
38.
Sergeeva M, Ubl JJ, Reiser G. Disruption of actin cytoskeleton in cultured rat astrocytes suppresses ATP- and bradykinin-induced [Ca(2+)](i) oscillations by reducing the coupling efficiency between Ca(2+) release, capacitative Ca(2+) entry, and store refilling. Neuroscience. 2000;97:765–9.PubMed
39.
Schreiner AE, Durry S, Aida T, Stock MC, Ruther U, Tanaka K, et al. Laminar and subcellular heterogeneity of GLAST and GLT-1 immunoreactivity in the developing postnatal mouse hippocampus. J Comp Neurol. 2014;522:204–24.PubMed
40.
Verkhratsky A, Nedergaard M, Hertz L. Why are Astrocytes Important? Neurochem Res. 2014;40:389–401.PubMed
41.
Muramatsu T, Uekusa T, Masaoka T, Saitoh M, Hashimoto S, Abiko Y, et al. Differential expression and localization of connexins 26 and 43 in the rat gingival epithelium. Arch Histol Cytol. 2008;71:147–54.PubMed
42.
Tu CL, Chang W, Bikle DD. The role of the calcium sensing receptor in regulating intracellular calcium handling in human epidermal keratinocytes. J Invest Dermatol. 2007;127:1074–83.PubMed
43.
Spohn D, Rossler OG, Philipp SE, Raubuch M, Kitajima S, Griesemer D, et al. Thapsigargin induces expression of activating transcription factor 3 in human keratinocytes involving Ca2+ ions and c-Jun N-terminal protein kinase. Mol Pharmacol. 2010;78:865–76.PubMed
44.
Takada H, Furuya K, Sokabe M. Mechanosensitive ATP release from hemichannels and Ca(2)(+) influx through TRPC6 accelerate wound closure in keratinocytes. J Cell Sci. 2014;127:4159–71.PubMed
45.
Barr TP, Albrecht PJ, Hou Q, Mongin AA, Strichartz GR, Rice FL. Air-stimulated ATP release from keratinocytes occurs through connexin hemichannels. PLoS One. 2013;8:e56744.PubMedCentralPubMed
46.
Genever PG, Maxfield SJ, Kennovin GD, Maltman J, Bowgen CJ, Raxworthy MJ, et al. Evidence for a novel glutamate-mediated signaling pathway in keratinocytes. J Invest Dermatol. 1999;112:337–42.PubMed
47.
Tonon R, D'Andrea P. Interleukin-1beta increases the functional expression of connexin 43 in articular chondrocytes: evidence for a Ca2 + −dependent mechanism. J Bone Miner Res. 2000;15:1669–77.PubMed
48.
Mayan MD, Carpintero-Fernandez P, Gago-Fuentes R, Martinez-de-Ilarduya O, Wang HZ, Valiunas V, et al. Human articular chondrocytes express multiple gap junction proteins: differential expression of connexins in normal and osteoarthritic cartilage. Am J Pathol. 2013;182:1337–46.PubMedCentralPubMed
49.
Vittur F, Grandolfo M, Fragonas E, Godeas C, Paoletti S, Pollesello P, et al. Energy metabolism, replicative ability, intracellular calcium concentration, and ionic channels of horse articular chondrocytes. Exp Cell Res. 1994;210:130–6.PubMed
50.
Wilkins RJ, Fairfax TP, Davies ME, Muzyamba MC, Gibson JS. Homeostasis of intracellular Ca2+ in equine chondrocytes: response to hypotonic shock. Equine Vet J. 2003;35:439–43.PubMed
51.
Zhang J, Zhang HY, Zhang M, Qiu ZY, Wu YP, Callaway DA, et al. Connexin43 hemichannels mediate small molecule exchange between chondrocytes and matrix in biomechanically-stimulated temporomandibular joint cartilage. Osteoarthritis Cartilage. 2014;22:822–30.PubMed
52.
Chi SS, Rattner JB, Matyas JR. Communication between paired chondrocytes in the superficial zone of articular cartilage. J Anat. 2004;205:363–70.PubMedCentralPubMed
53.
Koolpe M, Benton HP. Calcium-mobilizing purine receptors on the surface of mammalian articular chondrocytes. J Orthop Res. 1997;15:204–12.PubMed
54.
Piepoli T, Mennuni L, Zerbi S, Lanza M, Rovati LC, Caselli G. Glutamate signaling in chondrocytes and the potential involvement of NMDA receptors in cell proliferation and inflammatory gene expression. Osteoarthritis Cartilage. 2009;17:1076–83.PubMed
55.
Stains JP, Civitelli R. Gap junctions in skeletal development and function. Biochimica Et Biophysica Acta-Biomembranes. 2005;1719:69–81.
56.
Jorgensen NR, Henriksen Z, Brot C, Eriksen EF, Sorensen OH, Civitelli R, et al. Human osteoblastic cells propagate intercellular calcium signals by two different mechanisms. J Bone Miner Res. 2000;15:1024–32.PubMed
57.
Gupta A, Niger C, Buo AM, Eidelman ER, Chen RJ, Stains JP. Connexin43 enhances the expression of osteoarthritis-associated genes in synovial fibroblasts in culture. BMC Musculoskelet Disord. 2014;15:425.PubMedCentralPubMed
58.
Wall ME, Banes AJ. Early responses to mechanical load in tendon: role for calcium signaling, gap junctions and intercellular communication. J Musculoskelet Neuronal Interact. 2005;5:70–84.PubMed
59.
Maeda E, Ye S, Wang W, Bader DL, Knight MM, Lee DA. Gap junction permeability between tenocytes within tendon fascicles is suppressed by tensile loading. Biomech Model Mechanobiol. 2012;11:439–47.PubMed
60.
Waggett AD, Benjamin M, Ralphs JR. Connexin 32 and 43 gap junctions differentially modulate tenocyte response to cyclic mechanical load. Eur J Cell Biol. 2006;85:1145–54.PubMed
61.
Wall ME, Otey C, Qi J, Banes AJ. Connexin 43 is localized with actin in tenocytes. Cell Motil Cytoskeleton. 2007;64:121–30.PubMed
62.
Rohr S. Cardiac fibroblasts in cell culture systems: myofibroblasts all along?J Cardiovasc Pharmacol. 2011;57:389–99.PubMed
63.
Askar SF, Bingen BO, Swildens J, Ypey DL, van der Laarse A, Atsma DE, et al. Connexin43 silencing in myofibroblasts prevents arrhythmias in myocardial cultures: role of maximal diastolic potential. Cardiovasc Res. 2012;93:434–44.PubMed
64.
Liang W, McDonald P, McManus B, van Breemen C, Wang X. Characteristics of agonist-induced Ca2+ responses in diseased human valvular myofibroblasts. Proc West Pharmacol Soc. 2008;51:11–4.PubMed
65.
Riches K, Hettiarachchi NT, Porter KE, Peers C. Hypoxic remodelling of Ca2+ stores does not alter human cardiac myofibroblast invasion. Biochem Biophys Res Commun. 2010;403:468–72.PubMed
66.
Zeng QC, Guo Y, Liu L, Zhang XZ, Li RX, Zhang CQ, et al. Cardiac fibroblast-derived extracellular matrix produced in vitro stimulates growth and metabolism of cultured ventricular cells. Int Heart J. 2013;54:40–4.PubMed
67.
Gaspers LD, Thomas AP. Calcium signaling in liver. Cell Calcium. 2005;38:329–42.PubMed
68.
Balasubramaniyan V, Dhar DK, Warner AE, Vivien Li WY, Amiri AF, Bright B, et al. Importance of Connexin-43 based gap junction in cirrhosis and acute-on-chronic liver failure. J Hepatol. 2013;58:1194–200.PubMed
69.
Schlosser SF, Burgstahler AD, Nathanson MH. Isolated rat hepatocytes can signal to other hepatocytes and bile duct cells by release of nucleotides. Proc Natl Acad Sci U S A. 1996;93:9948–53.PubMedCentralPubMed
70.
Zimmermann B, Walz B. The mechanism mediating regenerative intercellular Ca2+ waves in the blowfly salivary gland. Embo Journal. 1999;18:3222–31.PubMedCentralPubMed
71.
Petersen OH, Tepikin AV. Polarized calcium signaling in exocrine gland cells. Annu Rev Physiol. 2008;70:273–99.PubMed
72.
Kielian T. Toll-like receptors in central nervous system glial inflammation and homeostasis. J Neurosci Res. 2006;83:711–30.PubMedCentralPubMed
73.
Forshammar J, Block L, Lundborg C, Biber B, Hansson E. Naloxone and ouabain in ultralow concentrations restore Na+/K + −ATPase and cytoskeleton in lipopolysaccharide-treated astrocytes. J Biol Chem. 2011;286:31586–97.PubMedCentralPubMed
74.
Hutchinson MR, Zhang Y, Brown K, Coats BD, Shridhar M, Sholar PW, et al. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). Eur J Neurosci. 2008;28:20–9.PubMedCentralPubMed
75.
Block L, Forshammar J, Westerlund A, Bjorklund U, Lundborg C, Biber B, et al. Naloxone in ultralow concentration restores endomorphin-1-evoked Ca(2)(+) signaling in lipopolysaccharide pretreated astrocytes. Neuroscience. 2012;205:1–9.PubMed
76.
Gorina R, Font-Nieves M, Marquez-Kisinousky L, Santalucia T, Planas AM. Astrocyte TLR4 activation induces a proinflammatory environment through the interplay between MyD88-dependent NFkappaB signaling, MAPK, and Jak1/Stat1 pathways. Glia. 2011;59:242–55.PubMed
77.
Kleveta G, Borzecka K, Zdioruk M, Czerkies M, Kuberczyk H, Sybirna N, et al. LPS induces phosphorylation of actin-regulatory proteins leading to actin reassembly and macrophage motility. J Cell Biochem. 2012;113:80–92.PubMed
78.
Arraes SM, Freitas MS, da Silva SV, de Paula Neto HA, Alves-Filho JC, Auxiliadora Martins M, et al. Impaired neutrophil chemotaxis in sepsis associates with GRK expression and inhibition of actin assembly and tyrosine phosphorylation. Blood. 2006;108:2906–13.PubMed
79.
Karpuk N, Burkovetskaya M, Fritz T, Angle A, Kielian T. Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity. J Neurosci. 2011;31:414–25.PubMedCentralPubMed
80.
Gegelashvili G, Schousboe A. High affinity glutamate transporters: regulation of expression and activity. Mol Pharmacol. 1997;52:6–15.PubMed
81.
Takaki J, Fujimori K, Miura M, Suzuki T, Sekino Y, Sato K. L-glutamate released from activated microglia downregulates astrocytic L-glutamate transporter expression in neuroinflammation: the ‘collusion’ hypothesis for increased extracellular L-glutamate concentration in neuroinflammation. J Neuroinflammation. 2012;9:275.PubMedCentralPubMed
82.
Hansson E, Westerlund A, Bjorklund U, Olsson T. mu-Opioid agonists inhibit the enhanced intracellular Ca(2+) responses in inflammatory activated astrocytes co-cultured with brain endothelial cells. Neuroscience. 2008;155:1237–49.PubMed
83.
Lundborg C, Hahn-Zoric M, Biber B, Hansson E. Glial cell line-derived neurotrophic factor is increased in cerebrospinal fluid but decreased in blood during long-term pain. J Neuroimmunol. 2010;220:108–13.PubMed
84.
Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015;16:358–72.PubMed
85.
Herrero MT, Estrada C, Maatouk L, Vyas S. Inflammation in Parkinson’s disease: role of glucocorticoids. Front Neuroanat. 2015;9:32.PubMedCentralPubMed
86.
Pihl-Jensen G, Tsakiri A, Frederiksen JL. Statin treatment in multiple sclerosis: a systematic review and meta-analysis. CNS Drugs. 2015;29:277–91.PubMed
87.
Sofroniew MV. Astrocyte barriers to neurotoxic inflammation. Nat Rev Neurosci. 2015;16:249–63.PubMed
88.
Chen L, Guo S, Ranzer MJ, DiPietro LA. Toll-like receptor 4 has an essential role in early skin wound healing. J Invest Dermatol. 2013;133:258–67.PubMedCentralPubMed
89.
90.
Ushio H, Nohara K, Fujimaki H. Effect of environmental pollutants on the production of pro-inflammatory cytokines by normal human dermal keratinocytes. Toxicol Lett. 1999;105:17–24.PubMed
91.
Lorenz W, Buhrmann C, Mobasheri A, Lueders C, Shakibaei M. Bacterial lipopolysaccharides form procollagen-endotoxin complexes that trigger cartilage inflammation and degeneration: implications for the development of rheumatoid arthritis. Arthritis Res Ther. 2013;15:R111.PubMedCentralPubMed
92.
Liu L, Gu H, Liu H, Jiao Y, Li K, Zhao Y, et al. Protective effect of resveratrol against IL-1beta-induced inflammatory response on human osteoarthritic chondrocytes partly via the TLR4/MyD88/NF-kappaB signaling pathway: an “in vitro study”. Int J Mol Sci. 2014;15:6925–40.PubMedCentralPubMed
93.
McNearney TA, Ma Y, Chen Y, Taglialatela G, Yin H, Zhang WR, et al. A peripheral neuroimmune link: glutamate agonists upregulate NMDA NR1 receptor mRNA and protein, vimentin, TNF-alpha, and RANTES in cultured human synoviocytes. Am J Physiol Regul Integr Comp Physiol. 2010;298:R584–598.PubMedCentralPubMed
94.
Jean YH, Wen ZH, Chang YC, Hsieh SP, Lin JD, Tang CC, et al. Increase in excitatory amino acid concentration and transporters expression in osteoarthritic knees of anterior cruciate ligament transected rabbits. Osteoarthritis and Cartilage. 2008;16:1442–9.PubMed
95.
Bonnet CS, Williams AS, Gilbert SJ, Harvey AK, Evans BA, Mason DJ. AMPA/kainate glutamate receptors contribute to inflammation, degeneration and pain related behaviour in inflammatory stages of arthritis. Ann Rheum Dis. 2015;74:242–51.PubMedCentralPubMed
96.
Vincenzi F, Targa M, Corciulo C, Gessi S, Merighi S, Setti S, et al. Pulsed electromagnetic fields increased the anti-inflammatory effect of A(2)A and A(3) adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. PLoS One. 2013;8:e65561.PubMedCentralPubMed
97.
Lindner D, Zietsch C, Tank J, Sossalla S, Fluschnik N, Hinrichs S, et al. Cardiac fibroblasts support cardiac inflammation in heart failure. Basic Res Cardiol. 2014;109:428.PubMed
98.
Javkhlan P, Hiroshima Y, Azlina A, Hasegawa T, Yao CJ, Akamatsu T, et al. Lipopolysaccharide-Mediated Induction of Calprotectin in the Submandibular and Parotid Glands of Mice. Inflammation. 2011;34:668–80.PubMed
99.
Ingman WV, Glynn DJ, Hutchinson MR. Inflammatory mediators in mastitis and lactation insufficiency. J Mammary Gland Biol Neoplasia. 2014;19:161–7.PubMed
100.
Redfern RL, Patel N, Hanlon S, Farley W, Gondo M, Pflugfelder SC, et al. Toll-Like Receptor Expression and Activation in Mice with Experimental Dry Eye. Investigative Ophthalmology & Visual Science. 2013;54:1554–63.
101.
Zare-Bidaki M, Tsukiyama-Kohara K, Arababadi MK. Toll-like receptor 4 and hepatitis B infection: molecular mechanisms and pathogenesis. Viral Immunol. 2014;27:321–6.PubMed
102.
Perros F, Lambrecht BN, Hammad H. TLR4 signalling in pulmonary stromal cells is critical for inflammation and immunity in the airways. Respir Res. 2011;12:125.PubMedCentralPubMed
103.
Greenberg AS, Obin MS. Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr. 2006;83:461S–5S.PubMed
104.
Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–7.PubMed
105.
Bleau C, Karelis AD, St-Pierre DH, Lamontagne L. Crosstalk between intestinal microbiota, adipose tissue and skeletal muscle as an early event in systemic low-grade inflammation and the development of obesity and diabetes. Diabetes Metab Res Rev. 2014. doi:10.​1002/​dmrr.​2617.
106.
107.
Prasad M, Hermann J, Gabriel SE, Weyand CM, Mulvagh S, Mankad R, et al. Cardiorheumatology: cardiac involvement in systemic rheumatic disease. Nat Rev Cardiol. 2014;12:168–76.PubMed
108.
O'Conor CJ, Leddy HA, Benefield HC, Liedtke WB, Guilak F. TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading. Proc Natl Acad Sci U S A. 2014;111:1316–21.PubMedCentralPubMed
109.
Verkhratsky A, Reyes RC, Parpura V. TRP channels coordinate ion signaling in astroglia. Rev Physiol Biochem Pharmacol. 2014;166:1–22.PubMedCentralPubMed
110.
Smani T, Shapovalov G, Skryma R, Prevarskaya N, Rosado JA. Functional and physiopathological implications of TRP channels. Biochim Biophys Acta. 1853;2015:1772–82.
111.
Zhao P, Lieu T, Barlow N, Sostegni S, Haerteis S, Korbmacher C, et al. Neutrophil Elastase Activates Protease-activated Receptor-2 (PAR2) and Transient Receptor Potential Vanilloid 4 (TRPV4) to Cause Inflammation and Pain. J Biol Chem. 2015;290:13875–87.PubMed
112.
Fernandes ES, Awal S, Karadaghi R, Brain SD. TRP receptors in arthritis, gaining knowledge for translation from experimental models. The open pain journal. 2013;6:50–61.
113.
Yang CA, Chiang BL. Inflammasomes and human autoimmunity: A comprehensive review. J Autoimmun. 2015;61:1–8.PubMed
114.
Hansson E. Actin Filament Reorganization in Astrocyte Networks is a Key Functional Step in Neuroinflammation Resulting in Persistent Pain: Novel Findings on Network Restoration. Neurochem Res. 2014;40:372–9.PubMed
115.
Metadata
Title
Coupled cell networks are target cells of inflammation, which can spread between different body organs and develop into systemic chronic inflammation
Authors
Elisabeth Hansson
Eva Skiöldebrand
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2015
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/s12950-015-0091-2

Other articles of this Issue 1/2015

Journal of Inflammation 1/2015 Go to the issue

Research

A new turbidimetric immunoassay for serum calprotectin for fully automatized clinical analysers

Research

Milk-derived bioactive peptides inhibit human endothelial-monocyte interactions via PPAR-γ dependent regulation of NF-κB

Research

Role of the NLRP3 inflammasome in the transient release of IL-1β induced by monosodium urate crystals in human fibroblast-like synoviocytes

Short Report

Increased expression of the NLRP3 inflammasome components in patients with Behçet’s disease

Research

Sera from patients with active systemic lupus erythematosus patients enhance the toll-like receptor 4 response in monocyte subsets

Research

Expression of hedgehog signal pathway in articular cartilage is associated with the severity of cartilage damage in rats with adjuvant-induced arthritis
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

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