Acid sphingomyelinase-derived ceramide is not required for inflammatory cytokine signalling in murine macrophages

Carl L. Manthey, Edward H. Schuchman

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Sphingomyelin hydrolysis is induced in myeloid cell-lines by tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interferon gamma (IFN-γ). Ceramide, a product of sphingomyelin hydrolysis, recapitulates many of the cellular responses elicited by these cytokines, and this has led to the hypothesis that ceramide is a second messenger of cytokine signalling. Sphingomyelin hydrolysis is catalysed by an acid sphingomyelinase (ASMase) and one or more neutral sphingomyelinases (NSMase); both ASMase and NSMase are activated during cytokine signalling. In the present study, the contribution of ASMase to TNF-α, IL-1β, and IFN-γ signalling in murine macrophages was addressed. Cytokine-induced responses were compared in macrophages derived from the bone marrow of ASMase null and wild-type mice. Specifically, TNF-α- and IFN-γ-induced nitric oxide production and TNF-α- and IL-1β-induced expression of the α-chemokine, KC, were intact in ASMase null macrophages. Furthermore, TNF-α induction of p42/p44 ERK and p38-MAPK phosphorylation, c-jun kinase activation, and IκBα degradation were normal. Also normal in ASMase null macrophages was TNF-α-, IL-1β and IFN-γ-induced expression of a panel of early response genes. It is concluded that ASMase is non-essential for the inflammatory signals activated in murine macrophages by TNF-α, IL-1β and IFN-γ.

Original languageEnglish
Pages (from-to)654-661
Number of pages8
JournalCytokine
Volume10
Issue number9
DOIs
StatePublished - Sep 1998

Keywords

  • Ceramide
  • Interleukin 1
  • Macrophages
  • Signalling
  • Sphingomyelinase
  • Tumour necrosis factor

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