Mixed effects of TGF-beta on human airway epithelial-cell chemokine responses.
We investigated chemokine responses of human airway epithelial cells to transforming growth factor (TGF)-beta alone and in combination with tumor necrosis factor (TNF)-alpha or interferon (IFN)-gamma. TGF-beta selectively induced production of granulocyte-macrophage colony stimulating factor (GM-CSF) without significant coordinate expression of IL-8 or RANTES. TNF-alpha induced expression of both IL-8 and GM-CSF, without detectable production of RANTES. TGF-beta synergistically enhanced GM-CSF production with TNF-alpha, but suppressed production and release of IL-8. IFN-gamma induced RANTES production and release; TGF-beta synergistically enhanced RANTES release induced by IFN-gamma, but had no effect on RANTES mRNA production. Taken together, these data demonstrate that TGF-beta may play a pivotal role in the responsiveness of airway epithelial cells to chemotactic cytokines, by selectively enhancing GM-CSF and RANTES production while suppressing IL-8 production. This profile of chemokine responses promoted by TGF-beta would favor eosinophil, lymphocyte and monocyte recruitment, hallmarks of chronic and allergic inflammation, over neutrophil sequestration.
Jagels
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The Scripps Research Institute, Department of Immunology/IMM-18, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Hugli
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D001980:Bronchi / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018946:Chemokine CCL5; D018925:Chemokines; D016209:Interleukin-8; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor