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

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

Research output: Contribution to journalArticle

107 Citations (Scopus)

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
StatePublished - 2000
Externally publishedYes

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Mitogen-Activated Protein Kinases
Gene expression
Muscle Cells
Cytokines
Gene Expression
Muscle
Interleukin-1
Interleukin-8
Smooth Muscle Myocytes
Smooth Muscle
Interleukin-6
Cells
Signal transduction
Immunosorbents
Polymerase chain reaction
RNA-Directed DNA Polymerase
Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Mitogen-activated protein kinases regulate cytokine gene expression in human airway myocytes. / Hedges, Jason; Singer, Cherie A.; Gerthoffer, William T.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 23, No. 1, 2000, p. 86-94.

Research output: Contribution to journalArticle

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