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To investigate the role of negative-regulatory factors A20,IRF-4 and TRAF4 of the toll-like receptor(TLR)signal pathways in immunological pathogenesis of Kawasaki disease(KD),48 children with Kawasaki disease,16 children with infectious disease(ID)and 16 age-matched healthy children were studied.Reverse-transcription PCR(RT-PCR)and real-time PCR were used to evaluate the expres- sion levels of negative-regulatory and effective factors in toll-like receptor 4(TLR4)signal pathways and proinflammatory factors in peripheral blood monocyte/macrophage(MC).In this study,expression levels of TLR4,MD-2,MyD88,IRAK-4,TRAF6,TAK1,t and TAB2 mRNA in KD group were detected to be elevated significantly during acute phase of KD.Transcription levels of negative-regulatory factors A20,IRF-4 and TRAF4 mRNA in KD or ID patients increased remarkably.However,expressions of IRF-4 and TRAF4 in KD patients were detected to be lower than that in ID patients,except that tran- scription levels of A20 were found to be higher than that in ID patients.Simultaneously,expressions of proinflammatory cytokines such as L-1β,IL-6 and TNF-αin KD patients were significantly elevated com- pared with those in ID patients.Furthermore,it was found that stimulation of lipopolysaccharide(LPS) remarkably up-regulated the expressions of negative-regulatory factors A20,IRF-4 and TRAF4 in KD pa- tients or healthy volunteers.The mRNA levels of all the three factors in KD patients were found to be lower than that in the latter.In addition,transcription levels of IRF-4 and TRAF4 in KD patients with coronary artery lesion(KD-CAL~+)were detected to be lower than those in KD patients without coronary artery lesion(KD-CAL~-)during acute phase,while that of A20 in KD-CAL~+ group were lower than that in the latter.And the levels of expressions of proinflammatory cytokines in KD-CAL~+ group were found to be higher than those in KD-CAL-group(P<0.01).These findings suggest that aberrant expression of negative-regulatory factors of TLRs signal pathways may be involved in immunological pathogenesis of Ka- wasaki disease.
To investigate the role of negative-regulatory factors A20, IRF-4 and TRAF4 of the toll-like receptor (TLR) signal pathways in immunological pathogenesis of Kawasaki disease (KD), 48 children with Kawasaki disease, 16 children with infectious disease ) and 16 age-matched healthy children were studied. Reverse-transcription PCR (RT-PCR) and real-time PCR were used to evaluate the expres- sion levels of negative-regulatory and effective factors in toll-like receptor 4 (TLR4) In this study, expression levels of TLR4, MD-2, MyD88, IRAK-4, TRAF6, TAK1, T and TAB2 mRNA in KD group were detected to be Expression of IRF-4 and TRAF4 in KD patients were detected to be lower than that that in ID patients, except that tran-scription levels of A20 were found t o be higher than that in ID patients. Simultaneously, expressions of proinflammatory cytokines such as L-1β, IL-6 and TNF-αin KD patients were significantly elevated com- pared with those in ID patients. Morerther, it was found that stimulation of The lipopolysaccharide (LPS) remarkably up-regulated the expressions of negative-regulatory factors A20, IRF-4 and TRAF4 in KD pa- tients or healthy volunteers.The mRNA levels of all the three factors in KD patients were found to be lower than that in the latter.In addition, transcription levels of IRF-4 and TRAF4 in KD patients with coronary artery lesion (KD-CAL ~ +) were detected to be lower than those in KD patients without coronary artery lesion (KD-CAL ~ -) during acute phase, while that of A20 in KD-CAL ~ + group were lower than that in the latter. And the levels of expressions of proinflammatory cytokines in KD-CAL ~ + group were found to be higher than those in KD-CAL-group (P <0.01) .These findings suggest that aberrant expression of negative-regulatory fac tors of TLRs signal pathways may be involved in immunological pathogenesis of Kawasaki disease.