[The role of activation of toll-like receptors in immunological pathogenesis of Kawasaki disease].
OBJECTIVE
A great deal of clinical evidence and epidemiologic data suggest that Kawasaki disease (KD) is correlated with an acute regulating imbalance of immunology. Lots of evidences in the past suggested that nuclear transcription factor-kappaB and preinflammation factors were up-regulated significantly in patients with KD. But the causative factors are still unknown. Toll-like receptors (TLRs) is a type I trans-membrane protein which could recognize ligands of pathogen microbes, activate the nuclear transcription factor-kappaB and promote gene transcription of pre-inflammation factors and co-stimulatory molecules on cell surface. Aberrant activation of signal pathway of TLRs could interfere with autoimmune tolerance and cause autoimmune diseases. The study was designed to investigate the role of signal transduction of TLRs on immunological pathogenesis of KD.


METHODS
Sixteen children with KD and 16 age-matched health children were studied. Reverse-transcription PCR (RT-PCR) and real-time PCR were used to evaluate the levels of TLRs 1 - 10, MD-2, MyD88, IL-1beta, IL-6 and IL-8 mRNA expressions in peripheral blood mononuclear cells, and expressions of TLRs 2, 4 and co-stimulatory molecules such as CD80 and CD86 in monocyte/macrophage were analyzed by flow cytometry.


RESULTS
(1) Compared with control group, the protein and mRNA levels of TLR4 in KD group were up-regulated significantly [(Real-time PCR: 325.22 +/- 50.34 vs. 2.20 +/- 0.23, P < 0.01); (flow cytometry: 15.96% +/- 5.94% vs. 3.21% +/- 0.62%, P < 0.01)], the difference being not significant as to other TLRs. (2) Transcriptional levels of MD-2 and Myd88 were significantly up-regulated in acute phase of KD (P < 0.01), and down-regulated after the treatment with intravenous gamma globulin therapy. (3) Expressions of co-stimulatory molecules and cytokines in monocyte/macrophage during acute phase of KD were higher than those of control group (P < 0.01).


CONCLUSIONS
Expressions of TLRs 4, MD-2 and Myd88 were up-regulated during acute phase in KD, suggesting that aberrant activation of TLRs 4 might be one of the initiating factors of immune aberrance in KD.
Wang
Guo-bing
GB
Department of Molecular Immunology, Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
Li
Cheng-rong
CR
Zu
Ying
Y
Yuan
Xiong-wei
XW
D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors