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Vitamin D and glucocorticoids differentially modulate chemokine expression in human airway smooth muscle cells
Author(s) -
Banerjee A,
Damera G,
Bhandare R,
Gu S,
LopezBoado Y S,
Panettieri R A,
Tliba O
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/bjp.2008.232
Subject(s) - calcitriol , chemokine , fluticasone , secretion , endocrinology , medicine , tumor necrosis factor alpha , cytokine , glucocorticoid , biology , vitamin d and neurology , immunology , inflammation , corticosteroid
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 properties in vitro in some cell types, its effects on ASM cells remain unclear. Here, we investigated whether 1α, 25‐dihydroxy vitamin D 3 (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