Glucocorticoids ablate IL-1β-induced β-adrenergic hyporesponsiveness in human airway smooth muscle cells

Paul E. Moore, Johanne D. Laporte, Sonia Gonzalez, Winfried Moller, Joachim Heyder, Reynold A. Panettieri, Stephanie A. Shore

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

We have previously reported that interleukin (IL)-1β decreases responsiveness of cultured human airway smooth muscle (HASM) cells to β- agonists. The purpose of this study was to determine whether glucocorticoids inhibit this IL-1β effect. Dexamethasone (Dex; 10-6 M) had no effect on concentration-related decreases in cell stiffness in response to isoproterenol (Iso) in control cells as measured by magnetic twisting cytometry but prevented the decreased responsiveness to Iso observed in IL- 1β (20 ng/ml)-treated cells. In addition, Dex had no effect on Iso- stimulated cAMP formation in control cells but prevented the IL-1β-induced reduction in Iso-stimulated cAMP formation. Similar effects on cell stiffness and cAMP responses were seen after pretreatment with the glucocorticoid fluticasone proprionate (FP). Dex and FP also prevented IL-1β-induced hyporesponsiveness to PGE2 stimulation. In contrast, neither IL-1β nor glucocorticoids had any effect on cell stiffness responses to dibutyryl cAMP. We have previously reported that the IL-1β effect on β-adrenergic responsiveness is mediated through cyclooxygenase-2 expression and prostanoid formation. Consistent with these observations, IL-1β-induced cyclooxygenase- 2 expression was virtually abolished by FP at concentrations of 10-10 M and greater, with a resultant decrease in PGE2 formation. However, Dex did not inhibit IL-1β-induced nuclear translocation of nuclear factor-κB or activator protein-1 in HASM cells. In summary, our results indicate that, in HASM cells, glucocorticoids alone do not alter responses to β-agonists but do inhibit IL-1β-induced β-adrenergic hyporesponsiveness. Glucocorticoids mediate this effect by inhibiting prostanoid formation but without altering nuclear factor-κB or activator protein-1 translocation.

Original languageEnglish (US)
Pages (from-to)L932-L942
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume277
Issue number5 21-5
DOIs
StatePublished - Nov 1999

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Keywords

  • Adenosine 3',5'-cyclic monophosphate
  • Cyclooxygenase-2
  • Interleukin-1β
  • Magnetic twisting cytometry
  • Nuclear factor-κB
  • Prostaglandin E
  • β-adrenergic receptor

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