title: Amelioration of concanavalin A-induced autoimmune hepatitis by magnesium isoglycyrrhizinate through inhibition of CD4(+)CD25(-)CD69(+) subset proliferation.
abstract: Magnesium isoglycyrrhizinate (MGL) is a new stereoisomer of glycyrrhizic acid, which is clinically used as a hepatoprotective medicine with more potent effects and less side effects than glycyrrhizic acid. This study was designed to evaluate the protective effects and possible mechanism of MGL against concanavalin A (Con A)-induced autoimmune hepatitis. Hepatitis was induced by Con A in C57/6J mice with or without MGL administration; injury score and serum ALT were evaluated. The CD4(+) T-cells were isolated from splenocytes and challenged with Con A after coculturing with MGL. The injury score was significantly improved in MGL-treated mice after Con A challenging for 12 and 24 hours compared with those merely challenged with Con A. Similar trends were observed in the serum levels of ALT and AST. The most interesting result was that MGL administration significantly decreased the frequency of CD4(+)CD25(-)CD69(+) T-cells rather than CD4(+)CD25(+)CD69(+) T-cells in peripheral blood mononuclear cells, after Con A challenging 12 and 24 hours. Moreover, the serum ALT levels were markedly correlated with the frequency of CD4(+)CD25(-)CD69(+) cells, but only weakly correlated with CD4(+)CD25(+)CD69(+) cells in peripheral blood mononuclear cells. More importantly, MGL (5 mg/mL) almost completely eliminated the proliferation of the CD25(-)CD69(+) subset in primary CD4(+) T-cells after Con A challenge. Compared with merely Con A-challenged mice, those with MGL administration significantly demonstrated decreased NALP3, NLRP6, and caspase-3 expression, in which the NALP3 and caspase-3 downregulated in a dose-dependent manner. Our results indicate that MGL may have potential as a therapeutic agent in autoimmune hepatitis by ameliorating liver injury. Its molecular mechanism may be involved in inhibiting CD4(+)CD25(-)CD69(+) subset proliferation and downregulating inflammasome expression in liver tissue.
authors: Beijing Ditan Teaching Hospital, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Qi
authors: Q
authors: Yang
authors: Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors: Jianwei
authors: J
authors: Wang
authors: Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors: Ran
authors: R
authors: Liu
authors: Beijing Ditan Teaching Hospital, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Zhiqiang
authors: Z
authors: Wang
authors: Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors: Yufeng
authors: Y
authors: Li
authors: Beijing Ditan Teaching Hospital, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Yifan
authors: Y
authors: Zhang
authors: Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors: Xiaohua
authors: X
authors: Hao
authors: Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors: Yubo
authors: Y
authors: Huang
authors: Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors: Wen
authors: W
authors: Xie
authors: Beijing Ditan Teaching Hospital, Peking University Health Science Center, Beijing, People's Republic of China; Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors: Hongshan
authors: H
authors: Wei
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019693:Hepatitis, Autoimmune / Q000276:immunology / Q000517:prevention & control*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003208:Concanavalin A; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D012503:Saponins; D014315:Triterpenes; D000099192:CD69 Antigens; C521270:18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate
keywords: adaptive immunity; autoimmune hepatitis; concanavalin A; drug therapy; mouse; regulatory T-cell