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p38 MAPK inhibitors attenuate pro-inflammatory cytokine production and the invasiveness of human U251 glioblastoma cells.

Abstract：

: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.

journal_name

J Neurooncol

journal_title

Journal of neuro-oncology

authors

Yeung YT,Bryce NS,Adams S,Braidy N,Konayagi M,McDonald KL,Teo C,Guillemin GJ,Grewal T,Munoz L

doi

10.1007/s11060-012-0875-7

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

35-44

issue

1

eissn

0167-594X

issn

1573-7373

journal_volume

109

pub_type

杂志文章

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