Anti-inflammatory effect of 1α,25-dihydroxyvitamin D3 in human coronary arterial endothelial cells: Implication for the treatment of Kawasaki disease

Kawasaki disease (KD) is an acute febrile vasculitis in childhood that is associated with inflammatory cytokines, in which the vascular inflammation results in damage to the coronary arteries. The active form of vitamin D, 1 alpha,25-dihydroxyvitamin D-3 {1 alpha,25-(OH)(2)D-3) exhibits anti-inflammatory activities. In this study, we determined the mRNA and protein expression of the vitamin D receptor in human coronary arterial endothelial cells (HCAEC) by RT-PCR and Western blotting, respectively. We examined whether or not 1 alpha,25-(OH)(2)D-3 inhibits the tumor necrosis factor-alpha (TNF-alpha)-induced activation of nuclear transcription factor-kappa B (NF-kappa B), which is essential for the expression of proinflammatory cytokines in HCAEC, by ELISA. In addition, we determined the inhibitory effect of 1 alpha,25-(OH)(2)D-3 on E-selectin expression induced by TNF-alpha in HCAEC by flow cytometry. RT-PCR revealed mRNA for the vitamin D receptor in HCAEC. Western blotting demonstrated vitamin D receptor protein in HCAEC. ELISA showed that pretreatment with 1 alpha,25-(OH)(2)D-3 significantly inhibited the TNF-alpha-induced NF-kappa B activation in HCAEC. Moreover, flow cytometry revealed that pretreatment with 1 alpha,25-(OH)(2)D-3 significantly inhibited the TNF-alpha-induced expression of E-selectin on HCAEC. Our results suggest that adjunctive 1 alpha,25-(OH)(2)D-3 may modulate the inflammatory response during KD vasculitis. (C) 2008 Elsevier Ltd. All rights reserved.