An immunoglobulin agent (IVIG) inhibits NF-kappaB activation in cultured endothelial cells of coronary arteries in vitro.
OBJECTIVE
Kawasaki disease (KD) is an acute febrile vasculitis of unknown etiology that may lead to cardiovascular disorders. High-dose intravenous immunoglobulin (IVIG) therapy is well established as a standard therapy for KD. Tumor necrosis factor-alpha (TNF-alpha) is responsible for the pathogenesis of acute KD. We examined whether or not IVIG inhibits TNF-alpha-induced activation of transcription factor NF-kappaB, a factor that is essential for the expression of proinflammatory cytokines, in human coronary artery endothelial cells (CAEC).


METHODS
The inhibitory effect of IVIG on NF-kappaB activation induced by TNF-alpha was evaluated by Western blot analysis and ELISA. Moreover, the inhibitory effects of IVIG on IkappaBalpha degradation, interleukin-6 (IL-6) production, and E-selectin expression induced by TNF-alpha were evaluated by Western blot analysis, ELISA, and flow cytometry, respectively.


RESULTS
Western blot analysis and ELISA demonstrated that IVIG inhibits NF-kappaB activation induced by TNF-alpha in CAEC. Moreover, IVIG inhibited IkappaBalpha degradation, IL-6 production, and E-selectin expression induced by TNF-alpha in CAEC.


CONCLUSIONS
The data suggest that IVIG inhibits NF-kappaB activation induced by TNF-alpha in CAEC, thereby possibly modulating IL-6 production and E-selectin expression.
Ichiyama
T
T
Department of Pediatrics, Yamaguchi University School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan. ichiyama@yamaguchi-u.ac.jp
Ueno
Y
Y
Isumi
H
H
Niimi
A
A
Matsubara
T
T
Furukawa
S
S
D001158:Arteries / Q000166:cytology; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016756:Immunoglobulins, Intravenous / Q000737:chemistry* / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D019040:E-Selectin; D020672:I-kappa B Proteins; D016756:Immunoglobulins, Intravenous; D015850:Interleukin-6; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha