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

Abstract

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