title: Complement C3a binding to its receptor as a negative modulator of Th2 response in liver injury in trichloroethylene-sensitized mice.
abstract: Trichloroethylene (TCE) is a major occupational health hazard and causes occupational medicamentosa-like dermatitis (OMLDT) and liver damage. Recent evidence suggests immune response as a distinct mode of action for TCE-induced liver damage. This study aimed to explore the role of the key complement activation product C3a and its receptor C3aR in TCE-induced immune liver injury. A mouse model of skin sensitization was induced by TCE in the presence and absence of the C3aR antagonist SB 290157. Liver function was evaluated by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in conjunction with histopathological characterizations. C3a and C3aR were detected by immunohistochemistry and C5b-9 was assessed by immunofluorescence. IFN-γ and IL4 expressions were determined by flow cytometry and ELISA. The total sensitization rate was 44.1%. TCE sensitization caused liver cell necrosis and inflammatory infiltration, elevated serum ALT and AST, expression of C3a and C3aR, and deposition of C5b-9 in the liver. IFN-γ and IL-4 expressions were up-regulated in spleen mononuclear cells and their serum levels were also increased. Pretreatment with SB 290157 resulted in more inflammatory infiltration in the liver, higher levels of AST, reduced C3aR expression on Kupffer cells, and decreased IL-4 levels while IFN-γ remained unchanged. These data demonstrate that blocking of C3a binding to C3aR reduces IL4, shifts IFN-γ and IL-4 balance, and aggravates TCE-sensitization induced liver damage. These findings reveal a novel mechanism whereby modulation of Th2 response by C3a binding to C3a receptor contributes to immune-mediated liver damage by TCE exposure.
authors: Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, PR China.
authors: Feng
authors: F
authors: Wang
authors: Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, PR China.
authors: Wan-sheng
authors: WS
authors: Zha
authors: Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, PR China.
authors: Jia-xiang
authors: JX
authors: Zhang
authors: Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, PR China.
authors: Shu-long
authors: SL
authors: Li
authors: Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, PR China.
authors: Hui
authors: H
authors: Wang
authors: Institute of Dermatology, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China.
authors: Liang-ping
authors: LP
authors: Ye
authors: Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, PR China; Institute of Dermatology, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China.
authors: Tong
authors: T
authors: Shen
authors: Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
authors: Chang-hao
authors: CH
authors: Wu
authors: Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, PR China; Institute of Dermatology, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China. Electronic address: zqxing@yeah.net.
authors: Qi-xing
authors: QX
authors: Zhu
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D003167:Complement Activation / Q000187:drug effects; D015926:Complement C3a / Q000378:metabolism*; D050776:Complement C5b / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D051379:Mice; D008807:Mice, Inbred BALB C; D011951:Receptors, Complement / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012997:Solvents / Q000633:toxicity*; D018418:Th2 Cells / Q000187:drug effects*; D014241:Trichloroethylene / Q000633:toxicity*
chemical_list: D001559:Benzhydryl Compounds; D011951:Receptors, Complement; C431907:SB 290157; D012997:Solvents; C085567:complement C3a receptor; D015847:Interleukin-4; D014241:Trichloroethylene; D015926:Complement C3a; D050776:Complement C5b; D007371:Interferon-gamma; D001120:Arginine
keywords: C3a; C3aR; Liver injury; Th2 cell; Trichloroethylene