Involvement of p38 and JNK MAPKs pathways in Substance P-induced production of TNF-α by peritoneal mast cells
Involvement of p38 and JNK MAPKs pathways in Substance P-induced production of TNF-α by peritoneal mast cells
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DOI：
10.1006/cyto.2002.0879
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发表时间：
2002-04-21
期刊：
影响因子：
3.8
通讯作者：
Lampiasi, N
中科院分区：
文献类型：
--
作者：
Azzolina, A;Guarneri, P;Lampiasi, N
肥大细胞在炎症和速发型过敏反应中起着核心作用。我们先前已经证明，P物质（SP）刺激大鼠腹膜肥大细胞（PMC）中TNF-α mRNA和蛋白质的表达。在本论文中，我们研究了肥大细胞激动剂诱导TNF-α产生是否涉及MAPKs信号通路。我们发现，早在PMC暴露于SP后5分钟，p38 MAPK和JNK的磷酸化被诱导。相反，p42/44 MAPK的磷酸化仅在暴露于SP 30分钟后发生，并且与SP诱导的TNF-α产生无关。高度特异性的p38 MAPK抑制剂SB 203580和PI-3 K阻断剂wortmannin，消除了SP诱导的TNF-α mRNA和蛋白水平的增加，并显示出减少SP介导的组胺分泌。此外，渥曼青霉素减少SP介导的JNK磷酸化。结果表明，P物质诱导大鼠PMC表达TNF-α和分泌组胺需要激活p38和JNK MAPK通路。此外，他们认为PI-3 K可能是SP诱导的炎症反应中JNK途径的上游成分。(C)2002爱思唯尔科技有限公司。保留所有权利。
Mast cells play a central role in both inflammation and immediate allergic reactions. We have previously shown that Substance P (SP) stimulates TNF-alpha mRNA and protein expression in rat peritonea] mast cells (PMC). In the present paper, we investigated whether the induction of TNF-alpha production by the mast cells agonist involves MAPKs signalling pathways. We found that as early as 5 min after PMC exposure to SP, phosphorylation of p38 MAPK and JNK was induced. On the contrary, phosphorylation of p42/44 MAPK occurred only after a 30 min exposure to SP and did not correlate with SP-induced TNF-alpha production. The highly specific p38 MAPK inhibitor SB203580 and the blocker of PI-3K wortmannin, abolished SP-induced increase in TNF-alpha mRNA and protein levels and showed to reduce the SP-mediated histamine secretion. In addition, wortmannin reduced SP-mediated JNK phosphorylation. The results reveal that the induction of TNF-a expression and histamine exocytosis by exposure of rat PMC to substance P requires the activation of p38 and JNK MAPKs pathways. Moreover, they suggest PI-3K as a possible upstream component of JNK pathway in SP-induced inflammatory reactions. (C) 2002 Elsevier Science Ltd. All rights reserved.