p38丝裂原活化蛋白激酶／胞浆型磷脂酶A2途径介导炎症细胞模型中白细胞介素的生成

p38 MAPK/cPLA2 pathway mediates interleukins release in inflammatory cell model

目的探讨p38丝裂原活化蛋白激酶（p38MAPK）对白细胞介索-1β（IL-1β）、IL-6的调节作用，进一步明确可能涉及的下游信号分子。方法以脂多糖（LPS）诱导的HeLa细胞为炎症模型，分别利用p38 MAPK、胞浆型磷脂酶A2（cPLA2）及环氧化酶-2（COX-2）特异性抑制剂SB203580、AACOCF3和NS-398以及cPLA2反义寡核苷酸（SK7111），通过检测HeLa细胞中LPS诱导的磷酸化p38MAPK、cPLA2及COX-2活性或表达的改变，观察其与上清液中IL-1β、IL-6含量变化的关系。结果SB203580可以明显抑制p38 MAPK、cPLA2的活性以及IL-1β、IL-6的产生；AACOCF3也可下调cPLA2活性以及IL-1β和IL-6的生成，且呈剂量依赖关系；而在HeLa细胞中几乎检测不到cPLA2下游信号分子COX-2的表达，也未观察到NS-398对IL-1β、IL-6表达的作用。结论在HeLa细胞中，p38MAPK／cPLA2途径介导LPS诿导细诱导细胞因子IL-1β和IL-6，而作为cPLA2下游酶之一的COX-2并没有参与此调节过程。

Objective To explore the underlying mechanism of lipopolysaecharide （LPS）-induced interleukin - 1/3 （IL - 1/3） and IL - 6 release via p38 mitogen activated protein kinase （MAPK） pathway in HeLa cells for further identification of involved down-stream message factors. Methods HeLa cells were challenged with LPS to reproduce inflammatory cell model. The activity or expression of p38 MAPK, eytosolic phospholipase A2 （cPLA2） and COX - 2, was inhibited with pretreatment of inflammatory HeLa cells with the inhibitors （SB203580, AACOCF3, NS- 398） or transfected with the cPLA2 antisense oligonucleotide （SK7111）, then the activities and/or expression of p38 MAPK, cPLA2, COX- 2, and relationship with levels of IL - 1β and IL - 6 supernatants were determined in each group. Results SB203580 obviously down regulated the activities of p38 and cPLA2, as well as the release of IL - 1β and IL - 6. AACOCF3 and SK7111 blocked dose-dependently the activity or expression of cPLA2, IL - 1β and IL - 6 production. However, the expression of COX - 2 could hardly be detected in HeLa cells, even after LPS treatment. At the same time, pre-treatment with NS - 398 had no effect on IL - 1β, IL - 6 production. Conclusion p38 MAPK/cPLA2 pathway mediates the expression of IL - 1β and IL 6 resulting from LPS treatment of HeLa cells, while COX - 2, as a down-stream enzyme of cPLA2 has no effect in this process.