The changes of negative-regulatory factors A20,IRF-4 and TRAF4 of toll-like receptor signal pathways in immunological pathogenesis of Kawasaki disease

摘要

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, 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.