中国循证儿科杂志2016，Vol.11Issue(6)：410-415,6.DOI:10.3969/j.issn.1673-5501.2016.06.002
急性期川崎病γ干扰素组蛋白乙酰化改变及意义初探
Changes and significances of histone 3 acetylation of IFN-γ gene during acute phase of Kawasaki disease
摘要
Abstract
Objective To investigate the changes and significances of histone 3 acetylation of IFN-γ gene in patients with acute Kawasaki disease( KD). Methods Children with KD were enrolled in Shenzhen Childrenˊs Hospital from February 2015 to June 2016,and sub-grouped as with or without coronary artery lesions( CAL). Age-matched healthy children attending routine physical examination were recruited as controls during the same period. Chromatin immunoprecipitation was performed to determine acetylation level of histone 3 of IFN-γ gene,and binding level of histone acetyltransferase p300 and deacetylase HDAC1/2 with IFN-γ gene. The proportion of CD4+IFN-γ+ cells(Th1)and protein levels of IFN-γ,pSTAT4,pSTAT5 and T-bet were analyzed by flow cytometry. Quantitative real-time PCR was used to evaluate the levels of IFN-γ,IL-2Rα/β,IL-12Rβ1/2,IL-18Rα/β and ITLR4 mRNA in CD4 + T cells. Plasma concentrations of IL-12,IL-2 and IL-18 were measured by enzyme-linked immunosorbent assay. Results ① Thirty-eight children with KD,including 16 children with CAL( KD-CAL+)and 22 children without CAL <br> (KD-CAL-),aged from 1 to 5. 2 years with a mean of 2. 9 years were recruited. The KD group consisted 20 males and 18 females,and 32 age-matched healthy children with 17 males were recruited as controls. No difference of age or sex was found between the two groups(P﹥0. 05). ② The proportion of Th1,expression levels of IFN-γ protein and mRNA,and acetylation levels of histone 3 of IFN-γ gene increased remarkably during acute KD(P﹤0. 05),and restored after IVIG therapy(P﹤0. 05). Meanwhile,all the four items aforementioned in KD-CAL+ subgroup were higher than those in KD-CAL- subgroup(P﹤0. 05).③ During acute KD,binding level of p300 with IFN-γgene was up-regulated significantly whereas binding level of HDAC1/2 with IFN-γ gene was down-regulated(P﹤0. 05),resulting in the higher ratio of p300/HDAC1/2 that was positive correlated with the acetylation level of IFN-γ gene in patients in acute KD(r=0. 52,P﹤0. 05). Moreover,binding level of p300 with IFN-γ gene and the ratio of p300/HDAC1/2 in KD-CAL+ subgroup were higher than those in KD-CAL- subgroup(P﹤0. 05),while a lower binding level of HDAC1/2 with IFN-γ gene was found in KD-CAL+ subgroup(P﹤0. 05). All the three items mentioned above restored remarkably after IVIG treatment(P﹤0. 05). ④In comparison with healthy controls,plasma concentration of inflammatory cytokines(IL-2,IL-12 and IL-18),expression levels of their receptors(IL-2Rα/β,IL-12Rβ1/2,IL-18Rα/β and TLR4)and downstream molecules(pSTAT5,pSTAT4,T-bet and MyD88)were elevated pronouncedly during acute KD(P ﹤0. 05),and restored to some extent after IVIG treatment(P﹤0. 05). Simultaneously,all the items mentioned before in KD-CAL+ subgroup were higher than those in KD-CAL- subgroup(P﹤0. 05). Conclusion Hyper-acetylation of histone of IFN-γgene might be one of the important factors contributing to immune dysfunction of KD.关键词
川崎病/IFN-γ/组蛋白乙酰化/Th1细胞/免疫Key words
Kawasakidisease/IFN-γ/Histoneacetylation/Thelpercell1type/Immune引用本文复制引用
梅洁花,崔冬,王勤,温鹏强,徐明国,唐根,刘琮,李成荣,王国兵..急性期川崎病γ干扰素组蛋白乙酰化改变及意义初探[J].中国循证儿科杂志,2016,11(6):410-415,6.基金项目
国家自然科学基金81102227，81300124；深圳市科技计划项目JCYJ20140416141331464，JCYJ20140416141331478， JCYJ20150403100317055；深圳市卫生计生系统科研项目201401053，201402042，201501032资助 （）
