calcitriol and Mucocutaneous-Lymph-Node-Syndrome

Kawasaki disease is an acute febrile vasculitis of childhood that is associated with elevated production of inflammatory cytokines, causing damage to the coronary arteries. The production of proinflammatory cytokines and expression of adhesion molecules in human coronary arterial endothelial cells (HCAECs) is regulated by nuclear transcription factor-κB (NF-κB) activation. We have previously reported that the active form of vitamin D, 1α,25-dihydroxyvitamin D(3) (1α,25-(OH)(2)D(3)), inhibits tumor necrosis factor-α (TNF-α)-induced NF-κB activation. In this study, we examined the anti-inflammatory effects of 1α,25-(OH)(2)D(3) on TNF-α-induced adhesion molecule expression (vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1)) and cytokine production (interleukin-6 (IL-6) and IL-8) in HCAECs. Pretreatment with 1α,25-(OH)(2)D(3) significantly inhibited TNF-α-induced VCAM-1 expression and IL-8 production in HCAECs. Our results suggest that adjunctive 1α,25-(OH)(2)D(3) therapy may modulate the inflammatory response during Kawasaki disease vasculitis.

Topics: Cell Adhesion; Coronary Vessels; Endothelial Cells; Endothelium, Vascular; Gene Expression Regulation; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Mucocutaneous Lymph Node Syndrome; RNA, Messenger; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; Vitamin D

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, 1alpha,25-dihydroxyvitamin D(3) {1alpha,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 1alpha,25-(OH)(2)D(3) inhibits the tumor necrosis factor-alpha (TNF-alpha)-induced activation of nuclear transcription factor-kappaB (NF-kappaB), which is essential for the expression of proinflammatory cytokines in HCAEC, by ELISA. In addition, we determined the inhibitory effect of 1alpha,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 1alpha,25-(OH)(2)D(3) significantly inhibited the TNF-alpha-induced NF-kappaB activation in HCAEC. Moreover, flow cytometry revealed that pretreatment with 1alpha,25-(OH)(2)D(3) significantly inhibited the TNF-alpha-induced expression of E-selectin on HCAEC. Our results suggest that adjunctive 1alpha,25-(OH)(2)D(3) may modulate the inflammatory response during KD vasculitis.

Topics: Animals; Anti-Inflammatory Agents; Blotting, Western; Chlorocebus aethiops; Coronary Vessels; COS Cells; E-Selectin; Endothelial Cells; Gene Expression Regulation; Humans; Jurkat Cells; Mucocutaneous Lymph Node Syndrome; NF-kappa B; Receptors, Calcitriol; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha; Vitamin D