Stimulus-dependent glucocorticoid-resistance of GM-CSF production in human cultured airway smooth muscle

Abstract

For a subpopulation of asthmatics, symptoms persist even with high doses of glucocorticoids. Glucocorticoids reduce the levels of the proinflammatory and fibrogenic cytokine, granulocytemacrophage colony-stimulating factor (GM-CSF) produced by human cultured airway smooth muscle (ASM). We have contrasted the effects of a synthetic glucocorticoid, dexamethasone, on thrombin- and IL-1α-stimulated GM-CSF production in human ASM cells. Although IL-1α stimulated three-fold higher levels of GM-CSF mRNA and protein compared to thrombin, dexamethasone concentration-dependently reduced IL-1α-stimulated GM-CSF more potently and to a greater extent than the response to thrombin. This pattern of glucoco..