In:
American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 281, No. 6 ( 2001-12-01), p. L1425-L1435
Abstract:
Numerous in vitro and in vivo studies have implicated the cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) as mediators of airway inflammation and therefore potentially important substances in the pathogenesis of asthma. In this study, we examined the mechanisms by which IL-1β and TNF-α affect inhibition of cell growth, G protein-coupled receptor (GPCR) desensitization, and the recently reported adenylyl cyclase sensitization in human airway smooth muscle (HASM) cultures. Our findings demonstrate that adenylyl cyclase sensitization is independent of cytokine-mediated cyclooxygenase type 2 (COX-2) and prostaglandin E 2 (PGE 2 ) induction, whereas COX-2 induction appears to be required for both growth inhibition and GPCR desensitization. However, GPCR desensitization was highly dependent on the presence of EGF during chronic treatment with cytokines, which could be explained by a synergistic effect of EGF on cytokine-mediated COX-2 and PGE 2 induction. Interestingly, various agents (including inhibitors of p42/p44 and p38 mitogen-activated protein kinase signaling) were significantly more effective in inhibiting cytokine-mediated PGE 2 induction, GPCR desensitization, and cell growth inhibition than in inhibiting COX-2 induction. These data demonstrate disparity in the requirement and sufficiency of COX-2 induction in promoting different functional effects of IL-1β and TNF-α in HASM.
Type of Medium:
Online Resource
ISSN:
1040-0605
,
1522-1504
DOI:
10.1152/ajplung.2001.281.6.L1425
Language:
English
Publisher:
American Physiological Society
Publication Date:
2001
detail.hit.zdb_id:
1477300-4
SSG:
12
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