Caspase-1 expression in multiple sclerosis plaques and cultured glial cells

Xue Ming, Weiping Li, Yasuhiro Maeda, Benjamin Blumberg, Sumul Raval, Stuart D. Cook, Peter C. Dowling

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Caspase-1 is responsible for processing inflammatory cytokines and is associated with the induction of apoptosis. Using RT-PCR, we found that caspase-1 mRNA transcripts from frozen brain extracts were significantly elevated in multiple sclerosis (MS) compared to controls. Immunohistochemical staining using a specific antiserum confirmed the marked up regulation of caspase-1 within acute and chronic MS plaques, while little staining was seen in control brains. In addition to the expected caspase-1 expression in microglia and infiltrating perivascular mononuclear cells, we found that cytoplasmic caspase-1 expression was sharply increased in the resident oligodendrocytes of MS lesions. The TUNEL reaction for fragmented DNA co-localized over an occasional caspase-1-expressing cell and large numbers of caspase-1-positive "corpses" were observed within phagocytic macrophages of an acute evolving MS lesion. Studies using an immortalized human oligodendroglial hybrid cell line exposed to cytokine challenge showed that death induction was blocked by the caspase-1-like inhibitor Z-YVAD-fmk, while the caspase-3-like inhibitor Z-DEVD-fmk was less effective. Cellular levels of procaspase-1 were reduced compared to controls in oligodendroglia induced to die by cytokine challenge, as judged by Western immunoblotting. Our results suggest that caspase-1 may play a role in the inflammatory and apoptotic processes associated with MS pathogenesis.

Original languageEnglish (US)
Pages (from-to)9-18
Number of pages10
JournalJournal of the Neurological Sciences
Volume197
Issue number1-2
DOIs
StatePublished - May 15 2002

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Keywords

  • Caspase-1
  • Cultures
  • Multiple sclerosis
  • Oligodendrocyte
  • Plaques

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