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Complement C3a binding to its receptor as a negative modulator of Th2 response in liver injury in trichloroethylene-sensitized mice.

Wang, F, Zha, WS, Zhang, JX, Li, SL, Wang, H, Ye, LP, Shen, T, Wu, CH and Zhu, QX (2014) Complement C3a binding to its receptor as a negative modulator of Th2 response in liver injury in trichloroethylene-sensitized mice. Toxicol Lett, 229 (1). pp. 229-239.

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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.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Wang, F
Zha, WS
Zhang, JX
Li, SL
Wang, H
Ye, LP
Shen, T
Zhu, QX
Date : 17 August 2014
DOI : 10.1016/j.toxlet.2014.06.841
Uncontrolled Keywords : C3a, C3aR, Liver injury, Th2 cell, Trichloroethylene
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:15
Last Modified : 24 Jan 2020 18:50

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