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

52 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
Externally publishedYes

Fingerprint

Caspase 1
Microglia
Caspases
Interleukin-1
Brain
Hippocampus
Interleukin-18
p38 Mitogen-Activated Protein Kinases
Peptide Hydrolases
Ischemia
Central Nervous System
Apoptosis
Cytokines
Inflammation
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Hypoxic induction of caspase-11/caspase-1/interleukin-1β in brain microglia. / Kim, Nam Gon; Lee, Heasuk; Son, Eunyung; Kwon, Oh Young; Park, Jae-Yong; Park, Jae Hoon; Cho, Gyeong Jae; Choi, Wan Sung; Suk, Kyoungho.

In: Molecular Brain Research, Vol. 114, No. 2, 10.06.2003, p. 107-114.

Research output: Contribution to journalArticle

Kim, NG, Lee, H, Son, E, Kwon, OY, Park, J-Y, Park, JH, Cho, GJ, Choi, WS & Suk, K 2003, 'Hypoxic induction of caspase-11/caspase-1/interleukin-1β in brain microglia', Molecular Brain Research, vol. 114, no. 2, pp. 107-114. https://doi.org/10.1016/S0169-328X(03)00135-9
Kim, Nam Gon ; Lee, Heasuk ; Son, Eunyung ; Kwon, Oh Young ; Park, Jae-Yong ; Park, Jae Hoon ; Cho, Gyeong Jae ; Choi, Wan Sung ; Suk, Kyoungho. / Hypoxic induction of caspase-11/caspase-1/interleukin-1β in brain microglia. In: Molecular Brain Research. 2003 ; Vol. 114, No. 2. pp. 107-114.
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