Effect of NF-κB on endothelial damage mediated by inflammatory cytokines in Kawasaki disease

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Objective Kawasaki disease (KD) is the leading cause of acquired heart diseases in children. Its etiology is unknown. In recent years, data have shown that the dysfunction of T cell and monocytes/macrophages plays a central role in the development of vasculitis. Nuclear factor-κB(NF-κB) is positioned to integrate information from immune signaling pathway that can regulate the function of T cell and monocytes/macrophages. But the role of NF-κB in endothelial damage of KD is unknown. Therefore, the objective of the study was to further explore the effects of NF-κB on the endothelial damage in KD. Methods Human umbilical vein endothelial cells were cultured in vitro and the production of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay ( ELISA). The proportion of apoptotic cells in endothelial cells induced by the supernatants of peripheral blood mononuclear cells (PBMCs) was detected by AnnexinⅤ/PI double-staining. Electrophoretic mobility shift assay (EMSA) was used to detect the activity of NF-κB. Results The levels of TNF-α, IL-1β and IL-6 were markedly increased in patients and the proportion of apoptotic cells in endothelial cells induced by the cultured supernatants of PBMCs was markedly elevated (38.45±7.80)% compared to (2.87±0.76)% in the control subjects. The apoptosis induced by the supernatants of cultured PBMCs could be reversed, to some degree, through alone anti- TNF-α, IL-1β or IL-6 monoclonal antibody (McAb), or the combination together. The activity of NF-κB in the activated PBMCs in patients with KD was distinctly increased and SN50, the blockade of NF-κB, could significantly inhibit the production of TNF-α, IL-1β, IL-6 and the apoptosis of endothelial cells induced by the supernatants of cultured PBMC. Conclusion NF-κB, which can trigger the transcription of inflammatory cytokines such, as TNF-α, IL-1β, IL-6, plays an important role in endothelial damage of KD. Key words: Mucocutaneous lymph node synrome; NF-κB; Cytokine; Endothelium, rascular