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.