Cultures of astrocytes and microglia express interleukin 18

Bruno Conti, Larry C.H. Park, Noel Y. Calingasan, Yoonseong Kim, Hocheol Kim, Youngmee Bae, Gary E. Gibson, Tong H. Joh

Research output: Contribution to journalArticlepeer-review

160 Scopus citations

Abstract

Interleukin 18 (IL-18 or interferon-γ inducing factor) is a recently discovered pro-inflammatory cytokine and powerful stimulator of the cell- mediated immune response. IL-18 is produced by several sources including monocytes/macrophages, keratinocytes and the zona reticularis and zona fasciculata of the adrenal cortex. IL-18 occurs in brain but its cellular source in the CNS has never been investigated. The presence of IL-18 and its response to stimulation in the brain was tested with primary cultures of microglia, astrocytes and hippocampal neurons. IL-18 mRNA was present in astrocytes and microglia, but not in neurons. The endotoxin lipopolysaccharide (LPS) did not affect IL-18 in astrocytes, but LPS robustly increased IL-18 mRNA in microglia. IL-18 protein was constitutively expressed in astrocytes and induced in microglia by LPS. The levels of interleukin-1β converting enzyme (ICE), an activating enzyme, and caspase 3 (CPP32), an inactivating enzyme, were assessed to investigate the presence of the appropriate processing enzymes in the cultured cells. ICE was present at constitutive levels in microglia and astrocytes suggesting that these cell types may produce and secrete matured IL-18. Active forms of CPP32 were not detectable in either cell type indicating the absence of a degradative pathway of IL-18. The present results demonstrate that microglia and astrocytes are sources of brain IL-18 and add a new member to the family of cytokines produced in the brain.

Original languageEnglish (US)
Pages (from-to)46-52
Number of pages7
JournalMolecular Brain Research
Volume67
Issue number1
DOIs
StatePublished - Apr 6 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Keywords

  • Astrocyte
  • BV2, brain
  • IL-18, lipopolysaccharide
  • Interleukin 18
  • Interleukin-1β converting enzyme
  • Microglia

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