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In particular, excessive deposition of C5 and C5b\u20109\u2010the membrane attack complex, which can generate significant tissue damage, was observed in the kidney tissue after TCE sensitization. The present study tested the hypothesis that anaphylatoxin C5a binding to its receptor C5aR mediates renal injury in TCE\u2010sensitized BALB\/c mice. BALB\/c mice were sensitized through skin challenge with TCE, with or without pretreatment by the C5aR antagonist W54011. Kidney histopathology and the renal functional test were performed to assess renal injury, and immunohistochemistry and fluorescent labeling were carried out to assess C5a and C5aR expressions. TCE sensitization up\u2010regulated C5a and C5aR expressions in kidney tissue, generated inflammatory infiltration, renal tubule damage, glomerular hypercellularity and impaired renal function. Antagonist pretreatment blocked C5a binding to C5aR and attenuated TCE\u2010induced tissue damage and renal dysfunction. TCE sensitization also caused the deposition of major pro\u2010inflammatory cytokines IL\u20102, TNF\u2010\u03b1 and IFN\u2010\u03b3 in the kidney tissue (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05); this was accompanied by increased expression of P\u2010p38, P\u2010ERK and P\u2010JNK proteins (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Pretreatment with the C5aR antagonist attenuated the increase of expression of P\u2010p38, P\u2010ERK and P\u2010JNK proteins (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) and also consistently reduced the TCE sensitization\u2010induced increase of IL\u20102, TNF\u2010\u03b1 and IFN\u2010\u03b3 (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). These data identify C5a binding to C5aR, MAP kinase activation, and inflammatory cytokine release as a novel mechanism for complement\u2010mediated renal injury by sensitization with TCE or other environmental chemicals. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3179","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T08:22:06Z","timestamp":1434702126000},"page":"271-284","source":"Crossref","is-referenced-by-count":33,"title":["Complement C5a\u2013C5aR interaction enhances MAPK signaling pathway activities to mediate renal injury in trichloroethylene sensitized BALB\/c mice"],"prefix":"10.1002","volume":"36","author":[{"given":"Jia\u2010xiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Occupational Health and Environment Health, School of Public Health Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010sheng","family":"Zha","sequence":"additional","affiliation":[{"name":"Anhui NO.2 Province People's Hospital  Hefei Anhui 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