Bradykinin receptor in immune-mediated renal tubular injury in trichloroethylene-sensitized mice: Impact on NF-κB signaling pathway

Abstract

xing Zhu (2018) Bradykinin receptor in immune-mediated renal tubular injury in trichloroethylene-sensitized mice: Impact on NF-κB signaling pathway, Journal of Immunotoxicology, 15:1, 126-136, ABSTRACT 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 etiology of the induced renal injury is not clear. Thus, this study explored any correlation between BK receptors and immune renal injury in TCE-sensitized mice by blocking the BK receptors B1R/B2R. BALB/c mice were sensitized (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-jB p65 subunit on tubular epithelial cells were all observed in TCE-sensitized mice. Serum levels of creatinine (Cr), microglobulin a1 and b2, along with mRNA levels for inflammatory cytokines and NF-jB p65 in kidneys, were all increased by 72 h after a final challenge. Highly selective antagonist pre-treatment blocked B2R and significantly attenuated TCEinduced changes. Blocking B1R or B2R attenuated release of pro-inflammatory cytokines and activation of NF-jB signaling pathway (as reflected in lower up-regulation of pIjB and nuclear NF-jB p65 subunit, and down-regulation of IjB 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-jB signaling pathway activation and amplified inflammatory cytokine release, which all likely contributed to TCE-induced immune renal injury. ARTICLE HISTORY

Inflammatory kidney injury in trichloroethylene hypersensitivity syndrome mice: Possible role of C3a receptor in the accumulation of Th17 phenotype

“…Consistently, our previous studies have also found that pathological changes in the kidney and impairment of renal function in TCE sensitized mice (Yang et al, 2018).…”

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“…У фібробластах вульви БK/B2R індукує активацію NF-κB, що посилює вивільнення IL-6 і викликає біль [35]. У суглобових хондроцитах людини та епітеліальних клітинах нирок БK індукує вивільнення запальних цитокінів, таких як IL-6 та IL-8, за допомогою сигнального механізму NF-κB [36]. [41,42], який призводить до розширення судин, збільшення проникності судин і гіпотензії.…”

Role and Mechanism of miR-181a-5p in Mice with Chronic Obstructive Pulmonary Disease by Regulating HMGB1 and the NF-κB Pathway

“…Based on the high expression of HMGB1 in lung tissues of COPD mice, the downstream NF-κB pathway of HMGB1 was investigated. The degradation of IκB and increased phosphorylation of IκB protein are the main manifestations of the activation of the NF-κB pathway [Yang et al, 2018;Chu et al, 2020]. The protein levels of p-IκBα and IκBα in lung tissues of COPD mice were tested by western blot.…”