Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1β production

Seon H. Kim, Carolyn J. Smith, Linda J. Van Eldik

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206 Citations (SciVal)

Abstract

In Alzheimer's disease (AD), chronically activated glia contribute to neuronal dysfunction through production of neuroinflammatory molecules like interleukin (IL)-1β. As a first step to address the signaling pathways important for pro-inflammatory cytokine induction, and whether different activators use distinct pathways, we tested the involvement of mitogen-activated protein kinase (MAPK) pathways in microglial IL-1β production. Microglial cultures stimulated with lipopolysaccharide, S100B, or beta-amyloid showed rapid activation of three different MAPKs (p38, ERK1/2, and JNK) and a later increase in IL-1β levels, consistent with a possible mechanistic relationship between MAPK and IL-1β. To more directly test this possibility, we stimulated microglia in the presence of selective MAPK inhibitors, and found that inhibition of each of the three MAPK pathways inhibited IL-1β production in a concentration-dependent manner. In addition, the relative importance of each MAPK to IL-1β production depended on the activating stimulus. These data demonstrate that MAPK pathways are important for microglial IL-1β production, and suggest that different glial activators use distinct sets of signaling pathways to induce the same disease-relevant end-point in microglia.

Original languageEnglish
Pages (from-to)431-439
Number of pages9
JournalNeurobiology of Aging
Volume25
Issue number4
DOIs
StatePublished - Apr 2004

Bibliographical note

Funding Information:
These studies were supported in part by NIH grants R37 AG13939, R01 AG20243, and P01 AG21184. S.H.K. is a postdoctoral scholar in the Drug Discovery Training Program supported by NIH grant T32 AG00260.

Keywords

  • Beta-amyloid
  • ERK
  • Interleukin-1
  • JNK
  • LPS
  • MAP kinase
  • Microglia
  • S100B
  • p38

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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