Mitogen-activated protein kinases regulate cytokine gene expression in human airway myocytes

Jason C. Hedges, Cherie A. Singer, William T. Gerthoffer

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

The signal transduction pathways regulating smooth-muscle gene expression and production of cytokines in response to proinflammatory mediators are undefined. Cultured human bronchial smooth-muscle cells were treated for 20 h with a cytokine cocktail containing interleukin (IL)-1β, tumor necrosis factor-α, and interferon-γ. A complementary DNA expression array containing 588 genes was used to follow cytokine-stimulated gene expression. The expression and secretion of the cytokines IL-1β, IL-6, and IL-8 significantly increased after 20 h of stimulation as measured by relative reverse transcriptase/polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting techniques. Expression of IL-6 and IL-8 was sensitive to SB203580, the specific inhibitor of p38 mitogen-activated protein (MAP) kinase and PD98059, an inhibitor of MAP kinase kinase. Expression of IL-1β was sensitive only to PD98059. Together, these results demonstrate that the p38 and extracellular signal-regulated protein kinase MAP kinase pathways are required for proinflammatory mediator-induced cytokine expression in airway myocytes. The generation of chemokines and cytokines in airway smooth muscle also provides evidence that smooth-muscle cells have the ability to contribute to the inflammatory response.

Original languageEnglish (US)
Pages (from-to)86-94
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2000

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ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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