May 15, 2001

Interleukin-1beta and rhinovirus sensitize adenylyl cyclase in human airway smooth-muscle cells

American Journal of Respiratory Cell and Molecular Biology
C K BillingtonI P Hall

Abstract

Rhinovirus (RV) is a major cause of wheezing in asthmatics and has been reported to cause beta2 adrenergic receptor hyporesponsiveness in human airway smooth muscle (HASM) via cellular secretion of interleukin (IL)-1beta. We studied the effects of IL-1beta and RV on cyclic adenosine monophosphate (cAMP) production in HASM cells. Chronic incubation with IL-1beta or RV caused a significant increase (approximately 3- and approximately 2-fold, respectively) in forskolin (FSK)-stimulated cAMP production, suggesting a sensitization of adenylyl cyclase (AC). The observed augmentation of FSK-stimulated cAMP formation by IL-1beta was completely abrogated by pretreatment with an IL-1 receptor antagonist or cycloheximide, demonstrating that the effect is mediated via the IL-1 receptor 1 (IL-1R1) and that de novo protein synthesis is required. In contrast, RV-induced AC sensitization was not mediated via the IL-1R1 but was observed to be protein kinase C-dependent. We suggest that the sensitization of AC observed after exposure to IL-1beta or RV infection is a cellular defense mechanism to promote pathways that induce relaxation in the inflamed airway.

  • References15
  • Citations13

References

  • References15
  • Citations13

Citations

Mentioned in this Paper

Picornaviridae Infections
Interleukins
Colforsin
Biochemical Pathway
Receptors, Interleukin-1 Type I
Sialoproteins
Muscle Cells
Interleukin-1
Agglutinogen 2, Bordetella Pertussis
Antagonist Muscle Action

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