Combined effect of tris(2-chloroethyl)phosphate and benzo (a) pyrene on the release of IL-6 and IL-8 from HepG2 cells via the EGFR-ERK1/2 signaling pathway
Combined effect of tris(2-chloroethyl)phosphate and benzo (a) pyrene on the release of IL-6 and IL-8 from HepG2 cells via the EGFR-ERK1/2 signaling pathway
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DOI：
10.1039/c7ra11273d
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发表时间：
2017-11
期刊：
影响因子：
3.9
通讯作者：
Youjian Zhang;Wenjuan Zhang;Jian Hou;Xian Wang;Hongyan Zheng;W. Xiong;Jing Yuan
中科院分区：
文献类型：
--
作者：
Youjian Zhang;Wenjuan Zhang;Jian Hou;Xian Wang;Hongyan Zheng;W. Xiong;Jing Yuan
磷酸三（2-氯乙基）酯（TCEP）和苯并（a）芘（BaP）共存于环境中。人类每天通过多种途径接触它们。每一种都引起肝毒性，这可能会增加其对人类健康的风险。然而，这两种化合物在体外联合毒性的机制仍不清楚。本研究旨在探讨TCEP和BaP联合作用于HepG 2细胞时炎症反应的分子机制。检测HepG 2细胞存活率、白细胞介素（IL）-6和IL-8在mRNA和蛋白水平的表达。结果表明，TCEP联合BaP可降低HepG 2细胞活力，上调IL-6和IL-8在mRNA和蛋白水平的表达。此外，EGFR（AG 1478）、ERK 1/2（U 0126）和p38 MAPK（SB 203580）的抑制剂在TCEP加BaP引起的炎症反应中显示出抗炎特性。AG 1478可抑制ERK 1/2的激活，但不抑制p38 MAPK的激活。这些结果表明，TCEP加BaP可能通过激活EGFR-ERK 1/2信号通路诱导HepG 2细胞的炎症反应。
Tris(2-chloroethyl)phosphate (TCEP) and benzo (a) pyrene (BaP) coexist in the environment. Humans are exposed to them via multiple routes every day. Each of them induces hepatotoxicity, which may increase their risk to human health. However, the mechanism underlying the combined toxicity of both compounds in vitro is still unclear. The present study aimed to investigate the molecular mechanism underlying the inflammatory response in the cotreatment of HepG2 cells with TCEP and BaP. The cell viability, and the expression of interleukin (IL)-6 and IL-8 at the mRNA and protein levels were measured in HepG2 cells. The results indicated that TCEP plus BaP decreased HepG2 cell viability, and up-regulated the expression of IL-6 and IL-8 at the mRNA and protein levels. Additionally, the inhibitors of EGFR (AG1478), ERK1/2 (U0126) and p38 MAPK (SB203580) displayed anti-inflammatory properties in the inflammatory response elicited by TCEP plus BaP. The activation of ERK1/2, but not p38 MAPK was inhibited by AG1478. These results indicated that TCEP plus BaP may induce an inflammatory response in HepG2 cells by the activation of the EGFR-ERK1/2 signaling pathway.