TGF-beta1 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 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)-beta1 to stimulate IL-8 release, cyclooxygenase (COX)-2 expression and PGE(2) generation in cultured human ASM cells and explored the role of COX products and COX-2 induction on IL-8 release. TGF-beta1 stimulated IL-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-beta1 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-beta1-induced PGE(2) release. These results show for the first time that TGF-beta1 stimulates IL-8 release, COX-2 induction, and PGE(2) generation in human ASM cells and that PGE(2) generation is not critical for TGF-beta1-induced IL-8 release. These findings suggest that TGF-beta1 may play an important role in the pathophysiology of asthma.
Fong
C Y
CY
Division of Respiratory Medicine, City Hospital, University of Nottingham, Nottingham NG5 1PB, United Kingdom.
Pang
L
L
Holland
E
E
Knox
A J
AJ
D000368:Aged; D000369:Aged, 80 and over; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004790:Enzyme Induction; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005938:Glucocorticoids; D016209:Interleukin-8; D007527:Isoenzymes; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D016212:Transforming Growth Factor beta; D003609:Dactinomycin; D003907:Dexamethasone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone