Inhibition of VCAM-1 expression in human bronchial epithelial cells by glucocorticoids

We have demonstrated previously that cytokines induce surface expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion mole cule-1 (ICAM-1) on BEAS-2B bronchial epithelial cells in vitro. The present studies demonstrate glucocorticoid inhibition of cytokine-induced VCAM-1 e xpression as detected using flow cytometry and Northern blot analysis. Seve ral commonly used inhaled glucocorticoids were tested for their ability to inhibit VCAM-1 and ICAM-1 expression. All glucocorticoids tested inhibited VCAM-1 expression in a dose-dependent manner. No inhibition of ICAM-1 expre ssion was observed, The most potent of the glucocorticoids tested for inhib ition of VCAM-1 expression were mometasone furoate and fluticasone propiona te (FP), which had IC50 values (i.e., concentrations at which each glucocor ticoid produced 50% inhibition) of under 10 pM, Budesonide, triamcinolone a cetonide, and beclomethasone dipropionate (BDP) had intermediate potency, a nd hydrocortisone and the BDP metabolite beclomethasone-17-monopropionate w ere the least potent of the steroids tested. Kinetic analysis of the abilit y of FP to inhibit VCAM-1 expression revealed that preincubation with FP fo r 3 h completely inhibited VCAM-1 expression induced by tumor necrosis fact or-alpha (TNF-alpha). FP inhibited VCAM-1 expression by 50% even when added as late as 6 h after stimulation with TNF-alpha. Using Northern blot analy sis, we confirmed inhibition of VCAM-1 and ICAM-1 messenger RNA (mRNA) expr ession by FP. Pretreatment with FP (10(-11) M to about 10(-7) M, 24 h) inhi bited TNF-alpha-induced VCAM-1 mRNA expression in BEAS-2B in a dose-depende nt manner, but did not inhibit expression of ICAM-1 mRNA. Studies with acti nomycin D indicate that FP treatment accelerated the degradation of TNF-alp ha-induced VCAM-1 mRNA. FP (10-7 M) also inhibited VCAM-1 mRNA expression i nduced by TNF-alpha in primary human bronchial epithelial cells as assessed by reverse transcription-polymerase chain reaction. These results suggest that suppression of epithelial VCAM-1 expression by glucocorticoids may con tribute to their anti-inflammatory effects.