Human Airway Smooth Muscle Cells Express and Release RANTES in Response to T Helper 1 Cytokines: Regulation by T Helper 2 Cytokines and Corticosteroids

Matthias John, Stuart J. Hirst, Peter J. Jose, Annette Robichaud, Neville Berkman, Christian Witt, Charles H.C. Twort, Peter J. Barnes, K. Fan Chung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

227 Scopus citations

Abstract

RANTES is a basic 8-kDa polypeptide of the C-C chemokine subfamily with strong chemotactic activity for eosinophils, lymphocytes, and monocytes. We determined the regulation of RANTES production by human airway smooth muscle cells in culture. While TNF-α, but not IFN-γ, increased RANTES mRNA expression and protein release, the combination of TNF-α and IFN-γ caused a greater degree of expression and release in a time- and dose-dependent manner. Sequential treatment of airway smooth muscle cells with TNF-α and IFN-γ showed that IFN-γ sensitized the cells to the stimulatory effect of TNF-α. Using a modified Boyden chamber technique, RANTES separated by reverse-phase liquid chromatography from cell culture supernatants of airway smooth muscle cells stimulated by TNF-α and IFN-γ showed a strong chemoattractant effect on human eosinophils, an effect inhibited by an anti-RANTES Ab. RANTES production induced by TNF-α and IFN-γ was inhibited partly by the Th2-derived cytokines, IL-4, IL-10, and IL-13, as well as by dexamethasone. Our studies indicate that, in addition to contractile responses and mitogenesis, airway smooth muscle cells have synthetic and secretory potential with the release of RANTES. They may participate in chronic airway inflammation by interacting with both Th1- and Th2-derived cytokines to modulate chemoattractant activity for eosinophils, activated T lymphocytes, and monocytes/macrophages.

Original languageAmerican English
Pages (from-to)1841-1847
Number of pages7
JournalJournal of Immunology
Volume158
Issue number4
StatePublished - 15 Feb 1997
Externally publishedYes

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