title: Endothelin-1 overexpression exacerbate experimental allergic encephalomyelitis.
abstract: BACKGROUND
  Multiple sclerosis (MS) is a CNS inflammatory demyelinating disorder. T helper 1 (Th1) and T helper 17 (Th17) cells are important in MS immunopathogenesis. Level of endothelin-1 (ET-1), a potent vasoconstrictor, is increased in sera of MS patients. We studied the role of ET-1 in experimental allergic encephalomyelitis (EAE), a MS animal model.
  
  
  METHODS
  EAE is induced in transgenic mice overexpressing endothelial ET-1 (TET-1), transgenic mice overexpressing astrocytic ET-1 (GET-1) and non-transgenic (NTg) mice by immunization with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. EAE scores, spinal cord histology, serum proinflammatory cytokines levels, and proinflammatory cytokines production from splenocytes of ET-1 transgenic and NTg mice with EAE were studied.
  
  
  RESULTS
  ET-1 transgenic mice developed more severe EAE than NTg with increased inflammation and demyelination in spinal cord. The mean maximum EAE scores for GET-1, TET-1 and NTg mice with EAE were 4.84, 4.31 and 4.05 respectively (p<0.05). Serum levels of IL-6, IL-17A, IFN-γ and TNF-α were higher in ET-1 transgenic than NTg mice with EAE (p<0.05) while serum IL-4 levels were similar. mRNA levels of IL-6, IL-17A, IFN-γ and TNF-α from cultured splenocytes were higher in ET-1-transgenic than NTg mice with EAE (p<0.05) while IL-4 mRNA levels were similar. Consistently, levels of IL-6, IL-17A, IFN-γ and TNF-α in culture media of splenocytes were higher in ET-1 transgenic than NTg mice with EAE (p<0.05) while IL-4 levels were similar.
  
  
  CONCLUSIONS
  Mice with endothelial or astrocytic ET-1 overexpression developed more severe EAE with increased splenic lymphocyte production of Th1 and Th17 proinflammatory cytokines.
authors.affiliation: University Department of Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong; Neuroimmunology and Neuroinflammation Research Laboratory, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong; Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Anatomy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Sookja Kim
authors.initials: SK
authors.lastname: Chung
authors.affiliation: University Department of Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong; Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
authors.affiliation: University Department of Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong; Neuroimmunology and Neuroinflammation Research Laboratory, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Shing-Cheong
authors.initials: SC
authors.lastname: Kwan
authors.affiliation: University Department of Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong; Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Philip Wing-Lok
authors.initials: PW
authors.lastname: Ho
authors.affiliation: Department of Anatomy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Patrick Ka-Kit
authors.initials: PK
authors.lastname: Yeung
authors.affiliation: University Department of Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong; Neuroimmunology and Neuroinflammation Research Laboratory, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong; Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong. Electronic address: koonho@hkucc.hku.hk.
authors.forename: Koon-Ho
authors.initials: KH
authors.lastname: Chan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D013116:Spinal Cord / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000187:drug effects
chemical_list: D016207:Cytokines; D019332:Endothelin-1; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)
keywords: Endothelin-1; Experimental allergic encephalomyelitis; Multiple sclerosis; Proinflammatory cytokines; Th1 cells; Th17 cells