P38 MAPK inhibitors attenuate pro-inflammatory cytokine production and the invasiveness of human U251 glioblastoma cells

Yiu To Yeung, Nicole S. Bryce, Seray Adams, Nady Braidy, Mari Konayagi, Kerrie L. McDonald, Charles Teo, Gilles J. Guillemin, Thomas Grewal*, Lenka Munoz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)35-44
Number of pages10
JournalJournal of Neuro-Oncology
Volume109
Issue number1
DOIs
Publication statusPublished - Aug 2012
Externally publishedYes

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