Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
J Neurooncol. 2012 Aug;109(1):35-44. doi: 10.1007/s11060-012-0875-7. Epub 2012 Apr 19.
Increasing evidence suggests that an inflammatory microenvironment promotes invasion by glioblastoma (GBM) cells. Together with p38 mitogen-activated protein kinase (MAPK) activation being regarded as promoting inflammation, we hypothesized that elevated inflammatory cytokine secretion and p38 MAPK activity contribute to expansion of GBMs. Here we report that IL-1β, IL-6, and IL-8 levels and p38 MAPK activity are elevated in human glioblastoma specimens and that p38 MAPK inhibitors attenuate the secretion of pro-inflammatory cytokines by microglia and glioblastoma cells. RNAi knockdown and immunoprecipitation experiments suggest that the p38α MAPK isoform drives inflammation in GBM cells. Importantly, p38 MAPK inhibition strongly reduced invasion of U251 glioblastoma cells in an inflammatory microenvironment, providing evidence for a p38 MAPK-regulated link between inflammation and invasiveness in GBM pathophysiology.
越来越多的证据表明，炎症微环境促进了脑胶质瘤（GBM）细胞的侵袭。由于 p38 丝裂原活化蛋白激酶（MAPK）的激活被认为可促进炎症，我们假设升高的炎症细胞因子分泌和 p38 MAPK 活性有助于 GBM 的扩张。在这里，我们报告说，在人类脑胶质瘤标本中，IL-1β、IL-6 和 IL-8 水平以及 p38 MAPK 活性升高，并且 p38 MAPK 抑制剂可减弱小胶质细胞和脑胶质瘤细胞中促炎细胞因子的分泌。RNAi 敲低和免疫沉淀实验表明，p38α MAPK 同工型驱动 GBM 细胞中的炎症。重要的是，p38 MAPK 抑制强烈减少了 U251 脑胶质瘤细胞在炎症微环境中的侵袭，为 GBM 发病机制中炎症与侵袭性之间存在 p38 MAPK 调节的联系提供了证据。
