Anti-inflammatory effect of 1alpha,25-dihydroxyvitamin D(3) 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, 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.
Suzuki
Yasuo
Y
Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
Ichiyama
Takashi
T
Ohsaki
Ayami
A
Hasegawa
Shunji
S
Shiraishi
Masahiro
M
Furukawa
Susumu
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D003331:Coronary Vessels / Q000166:cytology*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D019040:E-Selectin; D016328:NF-kappa B; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha; C118756:dihydroxy-vitamin D3; D014807:Vitamin D