Top

Journal of Neuroinflammation

Published in:

Open Access 01-12-2012 | Research

Corticotropin-releasing hormone and extracellular mitochondria augment IgE-stimulated human mast-cell vascular endothelial growth factor release, which is inhibited by luteolin

Authors: Shahrzad Asadi, Theoharis C Theoharides

Published in: Journal of Neuroinflammation | Issue 1/2012

Abstract

Background

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by varying degrees of dysfunctional social abilities, learning deficits, and stereotypic behaviors. Many patients with ASDs have ‘allergy-like’ symptoms and respond disproportionally to stress. We have previously shown that the peptide neurotensin (NT) is increased in the serum of young children with autism and that can stimulate extracellular secretion of mitochondrial (mt)DNA which was also increased in the serum of these children.

Methods

Human mast cells were stimulated by corticotropin-releasing hormone (CRH), mitochondrial DNA, IgE/anti-IgE, either for 24 hours to measure vascular endothelial growth factor (VEGF) release by ELISA or for 6 hours or quantitative PCR.

Results

CRH augmented IgE/anti-IgE-induced human mast-cell release of VEGF and it also induced the expression of IgE receptor (FcεRI) on mast cells. Moreover, sonicated mitochondria also augmented VEGF release, and this effect was blocked by the natural flavone luteolin.

Conclusion

These results indicate that stress and infection-mimicking extracellular mitochondrial components augment allergic inflammation that may be involved in the early pathogenesis of ASDs. Moreover, luteolin inhibits these processes and may be helpful in the treatment of ASDs.

Ashwood P, Wills S, Van de Water J: The immune response in autism: a new frontier for autism research. J Leukoc Biol 2006, 80:1–15.CrossRefPubMed

Atladottir HO, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, Parner ET: Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics 2009, 124:687–694.CrossRefPubMed

Theoharides TC, Kempuraj D, Redwood L: Autism: an emerging ’neuroimmune disorder’ in search of therapy. Exp Opinion on Pharmacotherapy 2009, 10:2127–2143.CrossRef

Theoharides TC, Kempuraj D, Tagen M, Conti P, Kalogeromitros D: Differential release of mast cell mediators and the pathogenesis of inflammation. Immunol Rev 2007, 217:65–78.CrossRefPubMed

Gurney JG, McPheeters ML, Davis MM: Parental report of health conditions and health care use among children with and without autism: National Survey of Children’s Health. Arch Pediatr Adolesc Med 2006, 160:825–830.CrossRefPubMed

Jyonouchi H, Geng L, Cushing-Ruby A, Quraishi H: Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study. J Neuroinflammation 2008, 5:52.CrossRefPubMedPubMedCentral

Bakkaloglu B, Anlar B, Anlar FY, Oktem F, Pehlivanturk B, Unal F, Ozbesler C, Gokler B: Atopic features in early childhood autism. Eur J Paediatr Neurol 2008, 12:476–479.CrossRefPubMed

Magalhaes ES, Pinto-Mariz F, Bastos-Pinto S, Pontes AT, Prado EA, Deazevedo LC: Immune allergic response in Asperger syndrome. J Neuroimmunol 2009, 216:108–112.CrossRefPubMed

Angelidou A, Alysandratos KD, Asadi S, Zhang B, Francis K, Vasiadi M, Kalogeromitros D, Theoharides TC: Brief report: “allergic symptoms” in children with autism spectrum disorders. more than meets the eye? J Autism Dev Disord 2011, 41:1579–1585.CrossRefPubMed

10.

White SW, Oswald D, Ollendick T, Scahill L: Anxiety in children and adolescents with autism spectrum disorders. Clin Psychol Rev 2009, 29:216–229.CrossRefPubMedPubMedCentral

11.

Cao J, Papadopoulou N, Kempuraj D, Boucher WS, Sugimoto K, Cetrulo CL, Theoharides TC: Human mast cells express corticotropin-releasing hormone (CRH) receptors and CRH leads to selective secretion of vascular endothelial growth factor. J Immunol 2005, 174:7665–7675.CrossRefPubMed

12.

Angelidou A, Francis K, Vasiadi M, Alysandratos K-D, Zhang B, Theoharides A, Lykouras L, Kalogeromitros D, Theoharides TC: Neurotensin is increased in serum of young children with autistic disorder. J Neuroinflammation 2010, 7:48.CrossRefPubMedPubMedCentral

13.

Fassio A, Evans G, Grisshammer R, Bolam JP, Mimmack M, Emson PC: Distribution of the neurotensin receptor NTS1 in the rat CNS studied using an amino-terminal directed antibody. Neuropharmacology 2000, 39:1430–1442.CrossRefPubMed

14.

Boucher J: Research Review: Structural language in autistic spectrum disorder - characteristics and causes. J Child Psychol Psychiatry 2012, 53:219–233.CrossRefPubMed

15.

Zhang B, Angelidou A, Alysandratos KD, Vasiadi M, Francis K, Asadi S, Theoharides A, Sideri K, Lykouras L, Kalogeromitros D, Theoharides TC: Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic children. J Neuroinflammation 2010, 7:80.CrossRefPubMedPubMedCentral

16.

Kempuraj D, Tagen M, Iliopoulou BP, Clemons A, Vasiadi M, Boucher W, House M, Wolferg A, Theoharides TC: Luteolin inhibits myelin basic protein-induced human mast cell activation and mast cell dependent stimulation of Jurkat T cells. Br J Pharmacol 2008, 155:1076–1084.CrossRefPubMedPubMedCentral

17.

Asadi S, Zhang B, Weng Z, Angelidou A, Kempuraj D, Alysandratos KD, Theoharides TC: Luteolin and thiosalicylate inhibit HgCl(2) and thimerosal-induced VEGF release from human mast cells. Int J Immunopathol Pharmacol 2010, 23:1015–1020.PubMed

18.

Kempuraj D, Saito H, Kaneko A, Fukagawa K, Nakayama M, Toru H, Tomikawa M, Tachimoto H, Ebisawa M, Akasawa A, Miyagi T, Kimura H, Nakajima T, Tsuji K, Nakahata T: Characterization of mast cell-committed progenitors present in human umbilical cord blood. Blood 1999, 93:3338–3346.PubMed

19.

McCary C, Tancowny BP, Catalli A, Grammer LC, Harris KE, Schleimer RP, Kulka M: Substance P downregulates expression of the high affinity IgE receptor (FcepsilonRI) by human mast cells. J Neuroimmunol 2010, 220:17–24.CrossRefPubMedPubMedCentral

20.

Kirshenbaum AS, Swindle E, Kulka M, Wu Y, Metcalfe DD: Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition. BMC Immunol 2008, 9:45.CrossRefPubMedPubMedCentral

21.

Theoharides TC, Angelidou A, Alysandratos KD, Zhang B, Asadi S, Francis K, Toniato E, Kalogeromitros D: Mast cell activation and autism. Biochim Biophys Acta 2012,1822(1):34–41.CrossRefPubMed

22.

Donelan J, Boucher W, Papadopoulou N, Lytinas M, Papaliodis D, Theoharides TC: Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process. Proc Natl Acad Sci USA 2006, 103:7759–7764.CrossRefPubMedPubMedCentral

23.

Gillott A, Standen PJ: Levels of anxiety and sources of stress in adults with autism. J Intellect Disabil 2007, 11:359–370.CrossRefPubMed

24.

Ercan F, San T, Cavdar S: The effects of cold-restraint stress on urinary bladder wall compared with interstitial cystitis morphology. Urol Res 1999, 27:454–461.CrossRefPubMed

25.

Esposito P, Chandler N, Kandere-Grzybowska K, Basu S, Jacobson S, Connolly R, Tutor D, Theoharides TC: Corticotropin-releasing hormone (CRH) and brain mast cells regulate blood–brain-barrier permeability induced by acute stress. J Pharmacol Exp Ther 2002, 303:1061–1066.CrossRefPubMed

26.

Theoharides TC, Konstantinidou A: Corticotropin-releasing hormone and the blood–brain-barrier. Front Biosci 2007, 12:1615–1628.CrossRefPubMed

27.

Esposito P, Gheorghe D, Kandere K, Pang X, Conally R, Jacobson S, Theoharides TC: Acute stress increases permeability of the blood–brain-barrier through activation of brain mast cells. Brain Res 2001, 888:117–127.CrossRefPubMed

28.

Theoharides TC, Singh LK, Boucher W, Pang X, Letourneau R, Webster E, Chrousos G: Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its pro-inflammatory effects. Endocrinology 1998, 139:403–413.PubMed

29.

Wright GL, Maroulakou IG, Eldridge J, Liby TL, Sridharan V, Tsichlis PN, Muise-Helmericks RC: VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase. FASEB J 2008, 22:3264–3275.CrossRefPubMedPubMedCentral

30.

Palmieri L, Persico AM: Mitochondrial dysfunction in autism spectrum disorders: Cause or effect? Biochim Biophys Acta 2010, 1797:1130–1137.CrossRefPubMed

31.

Weissman JR, Kelley RI, Bauman ML, Cohen BH, Murray KF, Mitchell RL, Kern RL, Natowicz MR: Mitochondrial disease in autism spectrum disorder patients: A cohort analysis. PLoS One 2008, 3:e3815.CrossRefPubMedPubMedCentral

32.

Frye RE, Rossignol DA: Mitochondrial dysfunction can connect the diverse medical symptoms associated with autism spectrum disorders. Pediatr Res 2011, 69:41R-47R.CrossRefPubMedPubMedCentral

33.

Chan DC: Mitochondria: dynamic organelles in disease, aging, and development. Cell 2006, 125:1241–1252.CrossRefPubMed

34.

Twig G, Hyde B, Shirihai OS: Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view. Biochim Biophys Acta 2008, 1777:1092–1097.CrossRefPubMed

35.

Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ: Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 2010, 464:104–107.CrossRefPubMedPubMedCentral

36.

Goines P, Van de Water J: The immune system’s role in the biology of autism. Curr Opin Neurol 2010, 23:111–117.CrossRefPubMedPubMedCentral

37.

Middleton E, Kandaswami C, Theoharides TC: The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacol Rev 2000, 52:673–751.PubMed

38.

Kempuraj D, Madhappan B, Christodoulou S, Boucher W, Cao J, Papadopoulou N, Cetrulo CL, Theoharides TC: Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells. Br J Pharmacol 2005, 145:934–944.CrossRefPubMedPubMedCentral

39.

Franco JL, Posser T, Missau F, Pizzolatti MG, Dos Santos AR, Souza DO, Aschner M, Rocha JB, Dafre AL, Farina M: Structure-activity relationship of flavonoids derived from medicinal plants in preventing methylmercury-induced mitochondrial dysfunction. Environ Toxicol Pharmacol 2010, 30:272–278.CrossRefPubMedPubMedCentral

40.

Theoharides TC: Luteolin as a therapeutic option for multiple sclerosis. J Neuroinflammation 2009, 6:29.CrossRefPubMedPubMedCentral

41.

Theoharides TC, Asadi S, Panagiotou JP: Effect of a luteolin formulation (NeuroProtek) on autism spectrum disorders-A case series. Int J Immunopathol and Pharmacol 2012,:. In press

42.

Theoharides TC, Zhang B: Neuro-inflammation, blood–brain barrier. Seizures and Autism J Neuroinflammation. 2011, 8:168.CrossRefPubMed

43.

Theoharides TC, Doyle R, Francis K, Conti P, Kalogeromitros D: Novel therapeutic targets for autism. Trends Pharmacol Sci 2008, 29:375–382.CrossRefPubMed

44.

Theoharides TC, Angelidou A, Alysandratos KD, Zhang B, Asadi S, Francis K, Toniato E, Kalogeromitros D: Mast cell activation and autism. Biochim Biophys Acta 1822, 2012:34–41.

45.

Deth R, Muratore C, Benzecry J, Power-Charnitsky VA, Waly M: How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis. Neurotoxicology 2008, 29:190–201.CrossRef

46.

Herbert MR: Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol 2010, 23:103–110.CrossRefPubMed

47.

Hamilton MJ, Hornick JL, Akin C, Castells MC, Greenberger NJ: Mast cell activation syndrome: a newly recognized disorder with systemic clinical manifestations. J Allergy Clin Immunol 2011, 128:147–152.CrossRefPubMed

Title: Corticotropin-releasing hormone and extracellular mitochondria augment IgE-stimulated human mast-cell vascular endothelial growth factor release, which is inhibited by luteolin
Authors: Shahrzad Asadi
Theoharis C Theoharides
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-9-85

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Corticotropin-releasing hormone and extracellular mitochondria augment IgE-stimulated human mast-cell vascular endothelial growth factor release, which is inhibited by luteolin

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2012

Regulation of podosome formation, microglial migration and invasion by Ca2+-signaling molecules expressed in podosomes

The immunology of traumatic brain injury: a prime target for Alzheimer’s disease prevention

Association of dimethylarginines and mediators of inflammation after acute ischemic stroke

Inhibition of Src kinase activity attenuates amyloid associated microgliosis in a murine model of Alzheimer’s disease

Acute injury in the peripheral nervous system triggers an alternative macrophage response

Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat