Induction of eotaxin expression and release from human airway smooth muscle cells by IL-1β and TNFα:: effects of IL-10 and corticosteroids

1 Eotaxin is a novel C-C chemokine with selective chemoattractant activity for eosinophiis. We determined whether eotaxin could be produced by human airway smooth muscle (HASM) cells in culture and examined its regulation by interleukin-10 (IL-10) and the corticosteroid, dexamethasone. 2 Stimulation of the cells with interleukin-1 beta (IL-1 beta) or tumour necrosis factor (TNF alpha) each at 10 ng ml(-1) induced the release of eotaxin protein with maximal accumulation by 24 h. Interferon-gamma (IFN gamma) alone at 10 ng ml(-1) had no effect and there was no synergy between these cytokines on the release of eotaxin. 3 Reverse phase high performance liquid chromatographic (HPLC) analysis of supernatents from cells treated with TNF alpha (10 ng ml(-1)) for 96 h showed immunoreactivity to eotaxin which eluted with the expected retention time of 34.5-35 min. 4 Both IL-1 beta and TNF alpha-induced release of eotaxin was not inhibited by dexamethasone (1 mu M), however IL-10 (10 ng ml(-1)) had a significant inhibitory effect. Dexamethasone and IL-10 did not inhibit the induction of eotaxin mRNA induced by IL-1 beta or TNF alpha. 5 Thus, human airway smooth muscle cells can release eotaxin and could be an important source of chemokine production during airway inflammatory events.