Hypoxic induction of caspase-11/caspase-1/interleukin-1β in brain microglia

Nam Gon Kim, Heasuk Lee, Eunyung Son, Oh Young Kwon, Jae Yong Park, Jae Hoon Park, Gyeong Jae Cho, Wan Sung Choi, Kyoungho Suk

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Caspase-11 is an inducible protease that plays an important role in both inflammation and apoptosis. Inflammatory stimuli induce and activate caspase-11, which is required for the activation of caspase-1 or interleukin-1β (IL-1β) converting enzyme (ICE). Caspase-1 in turn mediates the maturation of proinflammatory cytokines such as IL-1β, which is one of the crucial mediators of neurodegeneration in the central nervous system. Here, we report that hypoxic exposure of cultured brain microglia (BV-2 mouse microglia cells and rat primary microglial cultures) induces expression and activation of caspase-11, which is accompanied by activation of caspase-1 and secretion of mature IL-1β and IL-18. Hypoxic induction of caspase-11 was observed in both mRNA and protein levels, and was mediated through p38 mitogen-activated protein kinase pathway. Transient global ischemia in rats also induced caspase-11 expression and IL-1β production in hippocampus supporting our in vitro findings. Caspase-11-expressing cells in hippocampus were morphologically identified as microglia. Taken together, our results indicate that hypoxia induces a sequential event - caspase-11 induction, caspase-1 activation, and IL-1β release - in brain microglia, and point out the importance of initial caspase-11 induction in hypoxia-induced inflammatory activation of microglia.

Original languageEnglish
Pages (from-to)107-114
Number of pages8
JournalMolecular Brain Research
Volume114
Issue number2
DOIs
Publication statusPublished - 2003 Jun 10

Keywords

  • Hypoxia
  • Inflammation
  • Ischemia
  • Mitogen-activated protein kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Kim, N. G., Lee, H., Son, E., Kwon, O. Y., Park, J. Y., Park, J. H., Cho, G. J., Choi, W. S., & Suk, K. (2003). Hypoxic induction of caspase-11/caspase-1/interleukin-1β in brain microglia. Molecular Brain Research, 114(2), 107-114. https://doi.org/10.1016/S0169-328X(03)00135-9