| Background: Kawasaki disease is a common autoimmune vasculitis syndrome in childhood, which was reported widely among children in all world. The typical clinical manifestations are fever persistently, conjunctival injection, fissured lips, lymphadenopath, rash, and feet, periungual desquamation of toes and so on. Kawasaki disease is mainly the abnormal immune system activation and vascular endothelial extensive damage. Mainly for systemic involvement organs are heart arteries, especially small and medium-sized coronary artery, and some KD children have dangerous of coronary aneurysm, stenosis, even myocardial infarction. Currently KD has replaced rheumatic fever (RF) as the important cause in acquired heart disease, also become one of the important reasons in adult coronary artery damage .The medical researchers around the world researche the etiology, pathogenesis of KD constantly , including pathogenesis, etiology, therapy and prognosis, yet pathogenesis of KD was not illuminated now. Many clinical observations and epidemiological studies had suggested that immune dysfunction, which due to acute inflammation were implicated in the CAL of KD. It has been reported that a variety of bacteria, viruses, mycoplasma and their metabolites lead to uncontrol activations of immune cells, such as TNF-α, IL-6 increased significantly in KD, and especially increased IL-6 in KD ,which play important roles in blood vessel endothelium lesion. STAT3 as an important molecule participate in cytokines signal transduction. It is unclear that whether STAT3 participate in IL-6 mediated information process. So study mechanism of STAT3 in kawasaki disease can provide the scientific basis for its vasculitis damage mechanisms.STAT is a major mediated cytokines signaling pathway. STAT3 and activate the form of pSTAT3 has adjust a series of biological activities such as cell proliferation, apoptosis, differentiation and so on. STAT3 widely distribut in brain, liver , heart and thymus. STAT3 can be actiated by IL - 6, PDGF, the receptor tyrosine kinases and G protein. Previous studies have found, IL - 6 level of kawasaki disease in children with a more than ten times elevated. IL - 6 through activating STAT3 signaling pathways, participate in multiple inflammation, such as MMP - 9, IL - 17 to adjust the cellular immune response.This paper discusses express and activation significance of signal transduction and transcription factor 3 in KD children acute phase, aims to further explore KD immune pathogenesis.Objictive: 1. By means of summarizing 64 KD cases clinical datas to study clearly about the clinical features and danger of KD.2. Western blot technology carry out respectively to test peripheral blood KD and NC(normal children)STAT3, pSTAT3 protein distribution, preliminary learn the important role of STAT3 in KD.3. Real-time polymerase chain reaction (RT-PCR) was executed to assess the expression of STAT3 and after IL-6RmAb block, evaluate the expression of STAT3 in KD to further research the mechanism of STAT3 in Kawasaki disease, which can provide the scientific basis for treatment of kawasaki disease.4. Study STAT3 and clinical inflammation factors STAT3 correlation analysis to discusses the relationship between performance and clinical inflammation and significance.Methords: 1. Summary up 64cases clinical data of children with acute Kawasaki disease;2. Western blot analyze KD children in acute stage respectively before (IVIG), normal children in PBMCs STAT3, pSTAT3 distribution;3. Real-time polymerase chain reaction (RT-PCR) was executed to assess the expression of STAT3 before and after IL-6 stimlated in PBMCs; 4. with IL - 6R blockers blocking STAT3 signaling pathways, Real-time polymerase chain reaction (RT-PCR) was executed to assess the expression of STAT3 in PBMCs.Results: 1. In the 64 cases of KD, mean age (24. 17±15. 16) months, male 40 cases, female 24 cases. Be divided into coronary artery injury group (KDCAL +) and no damage group (KDCAL -), all the patients had a high fever, fever more than 5 day, of which the one patients with coronary aneurysm were 10 days; average thermal process (7. 43±1. 76) days, conjunctival injection:48 cases(75.0%); lymphadenopath:47cases(73.4%); strawberry tong: 40 casea(62.5%); fissured lips:58 cases (90.6%); rash: 38cases (59.3%);swelling, desquamation of hands and feet:44 cases(68.6%); the coronary artery lesion (CAL):40 cases(62.5%), in which, we had one patient with coronary aneurysm; laboratory examination had found: in the acute KD, the WBC was increased (15.87±11. 56×109/L), CRP significantly elevation(91.12±74. 36 mg/L),ESR significantly elevation (50. 78±27.83 mm/1 h),one patient with coronary aneurysm the ESR,CRP obvious increase; after IVIG treatment, these inflammatory markers decreased significantly(P<0.05).2. Before and after IL-6 stimulated, whole protein expression level of STAT3, pSTAT3 in patients with acute period is higher than normal controls. Before IL-6 stimulated, nucleoprotein expression level of STAT3, pSTAT3 in patients with acute period is no higher than normal controls. But after IL-6 stimulated, nucleoprotein expression level of STAT3, pSTAT3 in patients with acute period is higher than normal controls.3. Before and after IL-6 stimulated, the expression level of STAT3 mRNA in patients with acute period (1.15±0.19, 1.74±0.59) is higher than normal controls (0.56±0.37, 1.03±0.51) and infectious disease (ID) (1.07±0.21, 1.45±0.32), (P<0.05).4. After IL - 6R blockers blocking STAT3 signaling pathways , acute KD STAT3 mRNA level (0.99±0.15) significantly below the KD without IL-6R blocker (1.15±0.19, 1.74±0.59), and the infection fever children (1.07±0.21, 1.45±0.32),and still higher than normal children (0.56±0.37, 1.03±0.51), (P < 0.05).Conclusion: 1. Summarise of clinical datas: the 64 acute typical KD patients all had fever highly, had conjunctival injection, fissured lips, rash, swelling, lymphadenopath, desquamation of hands and feet; echocardiography examination can found coronary artery ectasia and coronary aneurysm; laboratory examination were found WBC, PLT, CRP increased, some had high level of immunoglobulin and myocaridial enzymes after IVIG, WBC, CRP, ESRdecreased obviously, only the PLT elevated slightly.2. Before and after IL-6 stimulated, whole protein expression level of STAT3, pSTAT3 in patients with acute period is higher than normal controls. Before IL-6 stimulated, nucleoprotein expression level of STAT3, pSTAT3 in patients with acute period is no higher than normal controls. But after IL-6 stimulated, nucleoprotein expression level of STAT3, pSTAT3 in patients with acute period is higher than normal controls. Speculate that abnormal activations of systemic vascular inflammatory have relate to activation of STAT3 and IL-6 plays a Key role in Positioning to nuclear and activation of STAT3,which can Start related genes transcription in nuclear,enhance inflammatory reaction.3. Real-time polymerase chain reaction (RT-PCR) was carry out to assess the mRNA expression of STAT3 before and after IL-6 stimlated in PBMCs. Before and after IL-6 stimulated, the expression level of STAT3 mRNA in patients with acute period is higher than normal controls and infectious disease (ID), the expression level of STAT3 mRNA in stimulated group are higher than no-stimulated group, which speculate that due to Kawasaki disease is a systemic vascular inflammatory diseases which relate to abmormal reaction of immunoreaction. Abnormal activation of immune cells in vivo especially a large number of lymphocytes lead to IL-6 release largely,which cause activation of STAT3 result in release of various inflammatory factors and chain of rings reactions, promote inflammation development and vascular injury in KD.4. After IL-6R mAb block STAT3, acute KD STAT3 mRNA level (0.99±0.15) significantly below the KD without IL-6R blocker and the infection fever children and still higher than normal children. This prompted that STAT3 mediated by IL-6 might play a main role in the early age of KD. |
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