TGF-b1 stimulates IL-8 release, COX-2 expression, and PGE2 release in human airway smooth muscle cells

Fong, Choong Yi, Linhua Pang, Elaine Holland, and Alan J. Knox. TGF-b1 stimulates IL-8 release, COX-2 expression, and PGE2 release in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 279: L201–L207, 2000.—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)-b1 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-b1 stimulated IL-8 release, COX-2 induction, and PGE2 generation in a concentrationand time-dependent manner. Maximal IL-8 release was achieved with 10 ng/ml of TGF-b1 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-b1-induced PGE2 release. These results show for the first time that TGF-b1 stimulates IL-8 release, COX-2 induction, and PGE2 generation in human ASM cells and that PGE2 generation is not critical for TGF-b1-induced IL-8 release. These findings suggest that TGF-b1 may play an important role in the pathophysiology of asthma.