title: Activation of the receptor for advanced glycation end products (RAGE) exacerbates experimental autoimmune myasthenia gravis symptoms.
abstract: RAGE belongs to immunoglobulin superfamily and serves as a ligand for various immunoregulatory molecules including S100B that has been demonstrated important to T cell mediated autoimmune diseases. In this context, we hypothesized that RAGE could also impact B cell mediated, T cell-dependent autoimmune diseases. This was tested using myasthenia gravis (MG) animal model, EAMG. We show that expression of both RAGE and S100B are increased during EAMG and the interaction between RAGE and S100B affected the Th1/Th2/Th17/Treg cell equilibrium, up-regulate AChR-specific T cell proliferation. Furthermore, addition of S100B in vitro stimulated splenocyte activity linked to COX-2 up-regulation. NS-398, a selective COX-2 inhibitor, effectively diminished S100B mediated activity of AChR-specific antibody secreting splenocytes. These findings suggested that a reciprocal relationship between RAGE and S100B promoted the development of EAMG, highlighting the importance of understanding the mechanisms of EAMG disease as a means of developing new therapies for the treatment of MG.
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang, 150081, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Mu
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Jinghua
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Xie
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.forename: Qingfei
authors.initials: Q
authors.lastname: Kong
authors.forename: Yumei
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhijuan
authors.initials: Z
authors.lastname: Han
authors.forename: Guangyou
authors.initials: G
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.forename: Guozhong
authors.initials: G
authors.lastname: Li
authors.forename: Hulun
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D066298:In Vitro Techniques; D008024:Ligands; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D000067759:Receptor for Advanced Glycation End Products; D011950:Receptors, Cholinergic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D015854:Up-Regulation
chemical_list: D001323:Autoantibodies; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D008024:Ligands; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D009578:Nitrobenzenes; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011950:Receptors, Cholinergic; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D013449:Sulfonamides; C110235:myelin basic protein 68-86; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat