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1 stimulates IL-8 release,
COX-2 expression, and PGE2
release in human airway smooth muscle cells
Division of Respiratory Medicine, City Hospital, University of Nottingham, Nottingham NG5 1PB, United Kingdom
We have recently shown that endogenous prostanoids are critical in
bradykinin-stimulated interleukin (IL)-8 release from human airway
smooth muscle (ASM) cells. In this study, we tested the ability of
transforming growth factor (TGF)-
1 to stimulate IL-8 release,
cyclooxygenase (COX)-2 expression and PGE2 generation in
cultured human ASM cells and explored the role of COX products and
COX-2 induction on IL-8 release. TGF-1 stimulated IL-8 release, COX-2 induction, and PGE2 generation in a concentration-
and time-dependent manner. Maximal IL-8 release was achieved with 10 ng/ml of TGF-1 after 16 h of incubation, which was inhibited by
the transcription inhibitor actinomycin D and the corticosteroid
dexamethasone but was not affected by the nonselective COX inhibitor
indomethacin and the selective COX-2 inhibitor NS-398 despite their
inhibition on TGF-1-induced PGE2 release. These results
show for the first time that TGF-1 stimulates IL-8 release, COX-2
induction, and PGE2 generation in human ASM cells and that
PGE2 generation is not critical for TGF-1-induced IL-8
release. These findings suggest that TGF-1 may play an important
role in the pathophysiology of asthma.
transforming growth factor-1; interleukin-8; cytokines; airway
inflammation; asthma; prostaglandin E2
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