THE EFFECTS OF NF-кB ON THE ENDOTHELIAL DAMAGE MEDIATED BY INFLAMMATORY CYTOKINES IN KAWASAKIDISEASE

Fu JR1, Li CR1, Zhou YD2

1Children’s Hospital of Shenzhen, Shenzhen, China

2Children’s Hospital of Chongqing, Chongqing, China.

 

Objective: To further explore the effects of nuclear factor-кB (NF-кB) on the endothelial damage mediated by inflammatory cytokines in kawasaki diseae (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 Annexin V/PI doublestaining. Electrophoretic mobility shift assay (EMSA) was used to detect the activity of nuclear factor-кB (NF-кB).

Results: The level of TNF-α、IL-1β、IL-6 were markedly increased in KD 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 inducted by the cultured supernatants of PBMCs could be reversed, to some degree, through alone anti-TNF-α、IL-1β、IL-6 monoclonal antibody (McAb) or combining together. The activity of NF-кB in the activated PBMCs in KD patients was distinctly increased and SN50, the blockade of NF-кB, could significantly inhibit both the production of TNF-α、IL-1β、IL-6 and the apoptosis of endothelial cells induced by the cultured supernatants of PBMC in KD patients.

Conclusion: NF-кB, which can trigger the transcription of inflammatory cytokines such as TNF-α、IL-1β、IL-6, play an important role in endothelial damage of KD.

 
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