TGF-beta 1 stimulates IL-8 release, COX-2 expression, and PGE(2) release in human airway smooth muscle cells

We have recently shown that endogenous prostanoids are critical in bradykin in-stimulated interleukin (IL)-8 release from human airway smooth muscle (A SM) cells. In this study, we tested the ability of transforming growth fact or (TGF)-beta 1 to stimulate IL-8 release, cyclooxygenase (COX)-2 expressio n and PGE(2) generation in cultured human ASM cells and explored the role o f COX products and COX-2 induction on IL-8 release. TGF-beta 1 stimulated I L-8 release, COX-2 induction, and PGE(2) generation in a concentration- and time-dependent manner. Maximal IL-8 release was achieved with 10 ng/ml of TGF-beta 1 after 16 h of incubation, which was inhibited by the transcripti on 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-beta 1-induced PGE(2 ) release. These results show for the first time that TGF-beta 1 stimulates IL-8 release, COX-2 induction, and PGE(2) generation in human ASM cells an d that PGE(2) generation is not critical for TGF-beta 1-induced IL-8 releas e. These findings suggest that TGF-beta 1 may play an important role in the pathophysiology of asthma.