Journal of Neuro-Oncology

, Volume 109, Issue 1, pp 35–44

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
Laboratory Investigation

DOI: 10.1007/s11060-012-0875-7

Cite this article as:
Yeung, Y.T., Bryce, N.S., Adams, S. et al. J Neurooncol (2012) 109: 35. doi:10.1007/s11060-012-0875-7

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.

Keywords

GlioblastomaTumour microenvironmentp38 MAPK inhibitorsInflammationInvasion

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Yiu To Yeung
    • 1
  • Nicole S. Bryce
    • 2
  • Seray Adams
    • 3
  • Nady Braidy
    • 3
  • Mari Konayagi
    • 1
  • Kerrie L. McDonald
    • 3
    • 4
  • Charles Teo
    • 5
  • Gilles J. Guillemin
    • 3
    • 6
  • Thomas Grewal
    • 1
  • Lenka Munoz
    • 7
  1. 1.Faculty of PharmacyUniversity of SydneySydneyAustralia
  2. 2.School of ChemistryUniversity of SydneySydneyAustralia
  3. 3.School of Medical SciencesUniversity of New South WalesSydneyAustralia
  4. 4.Cure for Life Neuro-Oncology Group, Lowy Cancer Research CentreUniversity of New South WalesSydneyAustralia
  5. 5.Centre for Minimally Invasive NeurosurgeryPrince of Wales Private HospitalSydneyAustralia
  6. 6.Department of Neuroimmunology, St. Vincent’s Centre for Applied Medical ResearchSt. Vincent’s HospitalDarlinghurstAustralia
  7. 7.School of Medical Sciences (Pharmacology)University of SydneySydneyAustralia