Role of Toll-Like-Receptor-4 Signal Transduction Pathway on Vascular Damage in Kawasaki Disease

Objective To evaluate the gene expression of several molecules in Toll-like-receptor-4(TLR4) signal transduction pathway in the monocytes /macrophages after getting stimulated by the serum of Kawasaki disease(KD) patients in the acute phase as well as by γ-globulin,and to investigate the role of TLR4 in endothelial damage of KD and possible mechanism of γ-globulin in the treatment of KD.Methods Forty children with KD and 10 cases age-matched healthy children were studied.The gene expression of several molecules in TLR4 signal transduction pathway in the monocytes macrophages was evaluated after getting stimulated by the serum of KD patients in the acute phase as well as by γ-globulin.Results The expressions of TLR4 mRNA,MyD88 mRNA,TRAF6 mRNA in the human mononuclear macrophage(THP-1) were upregulated in KD serum group than in healthy control group,and γ-globulin could abolish the effect of KD serum group on TLR4 mRNA,MyD88 mRNA,and TRAF6 mRNA expressions;there was no difference in TLR4 mRNA,MyD88 mRNA,TRAF6 mRNA and CD14 mRNA expressions between KD-non coronary artery damage(KD-CAL-) serum group and KD-coronary artery damage(KD-CAL+) serum group.Conclusions It is assumed that TLR4 pathway involves in vascular damage in KD,and blocking the TLR4 pathway may be one of the mechanisms of γ-globulin to treat KD.