Trichloroethylene (TCE) is known to induce skin disorders and multi-system dysfunction, but the mechanism of this multi-organ injury is not entirely clear. It was shown in a previous study that levels of pivotal end-products of the kallikrein-kinin system (KKS), i.e. bradykinin (BK) and BK receptors B1R/B2R, in the kidneys were increased by TCE exposure. Unfortunately, how BK and its receptors acted in the aetiology of the induced renal injury is not clear. Thus, this study explored any correlation between BK receptors and immune renal injury in TCE-sensitised mice by blocking the BK receptors B1R/B2R. BALB/c mice were sensitised (via skin) by TCE, with or without pre-treatment with a B1R or B2R antagonist. Renal lesions, increased expressions of B1R, B2R, Kim-1, Lipocalin-2, and NF-?B p65 subunit on tubular epithelial cells were all observed in TCE-sensitised mice. Serum levels of creatinine (Cr), microglobulin ?1 and ?2, along with mRNA levels for inflammatory cytokines and NF- ?B p65 in kidneys, were all increased by 72?h after a final challenge. Highly selective antagonist pre-treatment blocked B2R and significantly attenuated TCE-induced changes. Blocking B1R or B2R attenuated release of pro-inflammatory cytokines and activation of NF-?B signaling pathway (as reflected in lower up-regulation of pI?B and nuclear NF-?B p65 subunit, and down-regulation of I?B in the kidneys. These results provided evidence that TCE-sensitization caused KKS activation and enhanced the expression of B1R and B2R on tubular epithelial cells. This, in turn, accelerated NF-?B signaling pathway activation and amplified inflammatory cytokine release, which all likely contributed to TCE-induced immune renal injury.
Authors: Yang L, Zhang J, Li N, Xie H, Chen S, Wang H, Shen T, ; Full Source: Journal of Immunotoxicology. 2018 Dec;15(1):126-136. doi: 10.1080/1547691X.2018.1532974.