Induction of interleukin-1β-converting enzyme (ICE) in murine microglia by lipopolysaccharide

Jianhua Yao, Rodney W Johnson

Research output: Contribution to journalArticle

Abstract

Interleukin-1β (IL-1β) synthesized in the brain is thought to be involved in the behavioral response to LPS. In this study, we examined in microglia the ability of LPS to induce interleukin-1β-converting enzyme (ICE), the protease responsible for processing proIL-1β to its mature biologically active form. The murine microglial cell line, N13, and primary microglia which had been previously isolated from brains of 2-d-old endotoxin-responsive C3H/HeOuJ mice and endotoxin-resistant C3H/HeJ mice, were cultured in the presence of various concentrations of LPS. Oligonucleotide primers for ICE and GAPDH were used in RT-PCR to determine the levels of ICE mRNA in microglia. ICE mRNA was constitutively expressed in N13 cells and primary microglia from both C3H/HeOuJ and C3H/HeJ mice. Upon exposure to LPS, ICE mRNA levels were markedly elevated in N13 cells and in microglia from C3H/HeOuJ mice, but not in microglia from endotoxin-resistant C3H/HeJ mice. Western immunoblotting was used to determine if the increase in ICE mRNA induced by LPS was accompanied by an increase in ICE protein. A modest increase in immunoreactivity for the p45 ICE precursor protein was evident in N13 cells and primary microglia from C3H/HeOuJ mice following exposure to LPS. Because corticosteroids inhibit the synthesis and secretion of IL-1β, in a second experiment microglia were treated with LPS in the presence of dexamethasone (0, 10 and 100 μM). Dexamethasone inhibited the LPS-induced increase in ICE mRNA and protein in microglia from C3H/HeOuJ mice. These results indicate that LPS stimulates microglia to express ICE. That dexamethasone inhibited the expression of ICE, suggests that corticosteroids regulate the secretion of IL-1β by microglial cells, in part, by regulating the expression of ICE.

Original languageEnglish (US)
Pages (from-to)170-178
Number of pages9
JournalMolecular Brain Research
Volume51
Issue number1-2
DOIs
StatePublished - Nov 1 1997

Keywords

  • Caspase-1
  • Corticosteroid
  • Dexamethasone
  • ICE
  • Interleukin-1β-converting enzyme
  • Lipopolysaccharide
  • Microglia

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Induction of interleukin-1β-converting enzyme (ICE) in murine microglia by lipopolysaccharide'. Together they form a unique fingerprint.

  • Cite this