Ca2+ responses to interleukin 1 and tumor necrosis factor in cultured human skin fibroblasts: Possible implications for reye syndrome

Barbara E. Corkey, Jean François Geschwind, Jude T. Deeney, Daniel E. Hale, Steven D. Douglas, Laurie Kilpatrick

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Elevated concentrations of cytokines were found in the plasma of patients acutely ill with Reye syndrome (RS) but not in control subjects or recovered RS patients. To determine whether this disorder involves a genetically determined abnormal response to cytokines, the effects of tumor necrosis factor (TNF) and IL-1 on intracellular free Ca2+ were compared in cultured skin fibroblasts from control subjects and patients with RS. IL-1 and TNF caused rapid, transient, and concentration-dependent increases in cytosolic free Ca2+. The peak cytosolic free Ca2+ was greater and occurred at higher concentrations of IL-1 and TNF in patient cells than in cells from age-matched controls. In control cells, the Ca2+ transient diminished sharply with increasing amounts of IL-1 or TNF above the maximum stimulatory concentration. In contrast, in patient fibroblasts this bell-shaped curve of concentration dependency was much less apparent. Brady kinin-stimulated Ca2+ transients were similar in the two groups and did not exhibit the bell-shaped concentration dependency. Thus, plasma cytokine levels are elevated in RS patients and the Ca2+ response to cytokines is increased in cells derived from these patients. We propose that the increased response reflects a genetic defect in cytokine receptor-modulated signal transduction.

Original languageEnglish (US)
Pages (from-to)778-786
Number of pages9
JournalJournal of Clinical Investigation
Volume87
Issue number3
DOIs
StatePublished - 1991

Keywords

  • Bradykinin
  • Cyclic AMP
  • Cytokines
  • Phorbol esters
  • Signal transduction

ASJC Scopus subject areas

  • Medicine(all)

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