C5a Induces the Synthesis of IL-6 and TNF-α in Rat Glomerular Mesangial Cells through MAPK Signaling Pathways.
C5a Induces the Synthesis of IL-6 and TNF-α in Rat Glomerular Mesangial Cells through MAPK Signaling Pathways.
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C5a 通过 MAPK 信号通路诱导大鼠肾小球系膜细胞合成 IL-6 和 TNF-α
DOI：
10.1371/journal.pone.0161867
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Ji M;Lu Y;Zhao C;Gao W;He F;Zhang J;Zhao D;Qiu W;Wang Y
据报道，作为人系血管增殖性肾小球肾炎（MsPGN）动物模型的Thy-1肾炎（Thy-1N）大鼠的炎症反应有助于肾脏损害。除C5b-9复合物外，C5a也是一种有效的促炎介质，与各种肾病的严重程度相关。然而，C5a在Thy-1N大鼠中介导促炎细胞因子产生中的作用尚不明确。本研究首次测定了Thy-1N大鼠肾组织中C5a、白细胞介素-6 （IL-6）和肿瘤坏死因子-α (TNF-α)的水平。然后用重组大鼠C5a体外刺激大鼠肾小球系膜细胞（GMC），检测IL-6和TNF-α的表达。随后，在C5a诱导的GMC中，研究了丝裂原活化蛋白激酶（MAPK）信号通路（p38 MAPK、ERK1/2和JNK）的激活及其在调节IL-6和TNF-α产生中的作用。结果显示，Thy-1N大鼠肾组织中C5a、IL-6、TNF-α水平明显升高。体外刺激大鼠C5a可上调大鼠GMC中IL-6和TNF-α的表达，MAPK信号通路的激活参与了IL-6和TNF-α的诱导。机械上，p38 MAPK激活促进了IL-6的产生，而ERK1/2或JNK激活促进了C5a暴露的GMC中TNF-α的产生。综上所述，这些数据提示C5a通过激活MAPK信号通路诱导大鼠GMC中IL-6和TNF-α的合成。
Inflammatory response has been reported to contribute to the renal lesions in rat Thy-1 nephritis (Thy-1N) as an animal model of human mesangioproliferative glomerulonephritis (MsPGN). Besides C5b-9 complex, C5a is also a potent pro-inflammatory mediator and correlated to severity of various nephritic diseases. However, the role of C5a in mediating pro-inflammatory cytokine production in rats with Thy-1N is poorly defined. In the present studies, the levels of C5a, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were first determined in the renal tissues of rats with Thy-1N. Then, the expression of IL-6 and TNF-α was detected in rat glomerular mesangial cells (GMC) stimulated with our recombinant rat C5a in vitro. Subsequently, the activation of mitogen-activated protein kinase (MAPK) signaling pathways (p38 MAPK, ERK1/2 and JNK) and their roles in the regulation of IL-6 and TNF-α production were examined in the GMC induced by C5a. The results showed that the levels of C5a, IL-6 and TNF-α were markedly increased in the renal tissues of Thy-1N rats. Rat C5a stimulation in vitro could up-regulate the expression of IL-6 and TNF-α in rat GMC, and the activation of MAPK signaling pathways was involved in the induction of IL-6 and TNF-α. Mechanically, p38 MAPK activation promoted IL-6 production, while either ERK1/2 or JNK activation promoted TNF-α production in the GMC with exposure to C5a. Taken together, these data implicate that C5a induces the synthesis of IL-6 and TNF-α in rat GMC through the activation of MAPK signaling pathways.
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