Am. J. Respir. Cell Mol. Biol., Volume 18, Number 1, January, 1998 84-90

Expression and Release of Interleukin-8 by Human Airway Smooth Muscle Cells: Inhibition by Th-2 Cytokines and Corticosteroids

Mattheus John, Bo-Ting Au, Peter J. Jose, Sam Lim, Michael Saunders, Peter J. Barnes, Jane A. Mitchell, Maria G. Belvisi, and K. Fan Chung

Thoracic Medicine and Applied Pharmacology, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom

Interleukin (IL)-8 is a C-X-C chemokine that potently chemoattracts and activates neutrophils. We determined whether IL-8 could be produced by human airway smooth muscle cells in culture and examined its regulation. TNF- stimulated IL-8 mRNA expression and protein release in a time- and dose-dependent manner, whereas IFN- alone had no effect. Both cytokines together did not induce greater IL-8 release compared to TNF- alone. IL-1 was more potent in inducing IL-8 release and, together with TNF-, there was a synergistic augmentation of IL-8 release. IL-8 release induced by TNF- and IFN- was partly inhibited by the Th-2-derived cytokines IL-4, IL-10, and IL-13, as well as by dexamethasone. In addition to its contractile responses, airway smooth muscle cells have synthetic and secretory potential with the release of IL-8 and subsequent recruitment and activation of neutrophils in the airways. Release of IL-8 can be modulated by Th-2-derived cytokines and corticosteroids.

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