跳转至内容
Merck
  • Complement C3a binding to its receptor as a negative modulator of Th2 response in liver injury in trichloroethylene-sensitized mice.

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

Toxicology letters (2014-07-01)
Feng Wang, Wan-sheng Zha, Jia-xiang Zhang, Shu-long Li, Hui Wang, Liang-ping Ye, Tong Shen, Chang-hao Wu, Qi-xing Zhu
摘要

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.

材料
货号
品牌
产品描述

Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
三氯乙烯, ACS reagent, ≥99.5%
Sigma-Aldrich
L-精氨酸, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
布雷菲德菌素 A, from Penicillium brefeldianum, ≥99% (HPLC and TLC)
SAFC
L-精氨酸
Sigma-Aldrich
布雷菲德菌素 A, ≥99% (HPLC and TLC), BioXtra, for molecular biology
Sigma-Aldrich
小鼠 IL-4 ELISA 试剂盒, for cell and tissue lysates
Sigma-Aldrich
L-精氨酸, 99%, FCC, FG
Sigma-Aldrich
布雷菲德菌素 A, from Penicillium brefeldianum, Ready Made Solution, 10 mg/mL in DMSO
Sigma-Aldrich
L-精氨酸, reagent grade, ≥98%
Sigma-Aldrich
L-精氨酸, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
小鼠 IFN-γ ELISA 试剂盒, for serum, plasma, cell culture supernatant
Supelco
三氯乙烯 溶液, certified reference material, 5000 μg/mL in methanol
Sigma-Aldrich
Mouse IL-4 ELISA Kit, for serum, plasma and cell culture supernatant
Supelco
三氯乙烯, analytical standard, stabilized with 30 – 50 ppm Diisopropylamine
精氨酸, European Pharmacopoeia (EP) Reference Standard
USP
三氯乙烯 溶液, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
小鼠 IFN-γ ELISA 试剂盒, for cell and tissue lysates
Supelco
L-精氨酸, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
三氯乙烯, anhydrous, contains 40 ppm diisopropylamine as stabilizer, ≥99%
Sigma-Aldrich
三氯乙烯, JIS special grade, ≥99.5%