To investigate the role of negative-regulatory factors A20, IRF-d and TRAFd of the toll-like receptor （TLR） signal pathways in immunological pathogenesis of Kawasaki disease （KD）, 48 children with Kawasaki disease...To investigate the role of negative-regulatory factors A20, IRF-d and TRAFd 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 expression levels of negative-regulatory and effective factors in toll-like receptor d （TLRd） signal pathways and proinflammatory factors in peripheral blood monocyte/macrophage （MC）. In this study, expression levels of TLRd, MD-2, MyD88, IRAK-d, TRAF6, TAK1, TAB1 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 TRAFd mRNA in KD or ID patients increased remarkably. However, expressions of IRF-4 and TRAFd in KD patients were detected to be lower than that in ID patients, except that transcription 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-α in KD patients were significantly elevated compared 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-d and TRAFd in KD patients 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-d and TRAFd 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 Kawasaki disease.展开更多
文摘To investigate the role of negative-regulatory factors A20, IRF-d and TRAFd 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 expression levels of negative-regulatory and effective factors in toll-like receptor d （TLRd） signal pathways and proinflammatory factors in peripheral blood monocyte/macrophage （MC）. In this study, expression levels of TLRd, MD-2, MyD88, IRAK-d, TRAF6, TAK1, TAB1 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 TRAFd mRNA in KD or ID patients increased remarkably. However, expressions of IRF-4 and TRAFd in KD patients were detected to be lower than that in ID patients, except that transcription 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-α in KD patients were significantly elevated compared 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-d and TRAFd in KD patients 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-d and TRAFd 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 Kawasaki disease.
