The Mechanism Of Interleutin-27(IL-27)on Coronary Artery Lesions In Children With Kawasaki Disease

Background: The etiology and pathogenesis of Kawasaki disease(KD)is still unknown,and the prognosis of KD depends on the degree of coronary artery lesion(CAL).IL-27 is a recently found cytokine,involved in a variety of immune inflammatory disease.IL-27 and its receptor(IL-27R)binding can have a powerful role in immune regulation and exert double effect of proinflammatory and anti-inflammatory.We will explore whether IL-27 involved in the pathogenesis of KD and the mechanism.Methods:(1)We obtained blood samples from children with KD before intravenous immunoglobulin(IVIG)therapy.Levels of IL-27,IL-17 A,IL-10,IL-6,IL-1?,TNF-? were measured,including 4 groups: the normal control group(NC),febrile control(FC),KD without coronary arteries,KD with coronary arterial lesions.IL-27 and some cytokines were measured by ELISA.(2)C57BL/6 mice were injected with Lactobacillus casei cell wall extract(LCWE)to induce animal model of coronary arteritis.The relative levels of IL-27,WSX-1,IL-6 and TNF-? expression and inflammatory infiltrates in the coronary arteries were determined by ELISA and quantitative RT-PCR.Immunohistochemistry was used to detect the distribution of IL-27 and WSX-1.(3)The normal HCAECs,the WSX-1inhibited HCAECs were cultured with IL-27,and Real-time PCR was used to detect the expression levels of IL-6 and TNF-?,Western Blot was usedto detected the protein levels of signaling pathway.Results:(1)Levels of IL-27,IL-10,IL-17 A,IL-6,TNF-? were significantly elevated in KD group compared with febrile and control groups,especially in group of KD with CALs(P<0.05);There were positive relationship between serum levels of IL-27 and WBC,CRP,IL-10,IL-17 A,IL-6,TNF-? in children with KD(P<0.05).(2)The levels of IL-27,WSX-1,IL-6 and TNF-? were significantly elevated in the LCWE-injected mice(P<0.05).(3)Immunofluorescence showed that IL-27 R localized on the surface of HCAECs,but no IL-27.(4)Production of IL-6 and TNF-?were significantly increased in HCAECs cultured with Recombinant human IL-27(P<0.05).(5)The expression of TNF-? were significantly decreased in Stattic stimulsted HCAECs cultured with IL-27 and WSX-1inhibited HCAECs with IL-27,especially in the later.(P<0.05).(6)The expression of IL-6 were significantly decreased in group of IL-27 cultured with U0126 stimulsted HCAECs and group of IL-27-induced WSX-1inhibited HCAECs,it's more in the later.(P<0.05).(7)The protein expression of p-Stat3 and p-erk were significantly increased after IL-27 stimulated cultured with HCAECs(P<0.05).Conclusion:(1)IL-27 may involved in the pathogenesis of KD through induce the inflammatory cytokines secretion.(2)IL-27 may play a role in pathogesis of KD needs to binding WSX-1.(3)The mechanism of IL-27 binded WSX-1 inducing the inflammatory cytokines secretion may be through activating Stat3 and erk signaling pathway.