Vitamin D and glucocorticoids differentially modulate chemokine expression in human airway smooth muscle cells

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Abstract
Background and purpose: Chemokines play a critical role in the pathogenesis of asthma and facilitate the recruitment of inflammatory cells in the airways. Evidence now suggests that airway smooth muscle (ASM) may serve as a source of chemokines in inflamed airways. Although vitamin D has potent anti‐inflammatory propertiesin vitroin some cell types, its effects on ASM cells remain unclear. Here, we investigated whether 1α, 25‐dihydroxy vitamin D3(calcitriol) modulated chemokine production in ASM.Experimental approach: Human ASM cell cultures were derived from tracheal samples taken during surgery. ASM cells were treated with tumour necrosis factor alpha (TNFα) and/or interferon gamma (IFNγ) for 24 h in the presence of calcitriol and/or the glucocorticoid fluticasone added 2 h before. RANTES (regulated upon activation, normal T‐cell expressed and secreted), interferon‐inducible protein 10 (IP‐10) and fractalkine (FKN) levels in cell supernatants were measured by ELISA.Key results: In TNFα‐treated cells, calcitriol inhibited RANTES and IP‐10 secretion in a concentration‐dependent manner. FKN levels were negligible. In TNFα/IFNγ‐treated cells, whereas fluticasone or calcitriol alone partially inhibited RANTES secretion (by 38 and 20%, respectively), the combination of both drugs additively inhibited RANTES secretion (by 60%). No effect was observed on IP‐10 secretion. Whereas fluticasone enhanced FKN secretion (by 50%), calcitriol significantly decreased FKN levels (by 50%). Interestingly, calcitriol blocked the stimulatory effect of fluticasone on FKN secretion, which was inhibited by 60% with the combination of calcitriol and fluticasone.Conclusions and implications: These findings suggest that vitamin D uniquely modulates human ASM expression of chemokines and may exert some beneficial effects in the treatment of steroid‐resistant patients with asthma.British Journal of Pharmacology(2008)155, 84–92; doi:10.1038/bjp.2008.232; published online 16 June 2008