摘要
目的探讨白细胞介素37b重组蛋白(rmIL-37b)通过调节CD39/ATP轴抑制树突状细胞(DC)诱导类风湿性关节炎(RA)大鼠炎症反应的机制。方法将SD大鼠随机分为空白对照组(CTL)、CIA模型组、rmIL-37b 5μg/kg组、rmIL-37b 10μg/kg组,每组各10只。除了空白对照组外,其余大鼠采用含有卡介苗的完全弗氏佐剂和牛Ⅱ型胶原混合乳液免疫刺激,建立CIA模型。确定建模成功当天(D0),rmIL-37b组分别尾静脉注射5μg/kg、10μg/kg rmIL-37b;CTL组和CIA模型组注射相同体积的(1 ml/kg)生理盐水,连续给药15 d。免疫组化法检测滑膜组织Nod样受体蛋白3(NRPL3)炎症小体的表达,流式细胞术检测DC表型,另外试剂盒检测血清三磷酸腺苷(ATP)和免疫学指标。结果与CIA模型组相比,rmIL-37b 10μg/kg组大鼠足容积、AI值、NLRP3炎症小体表达量、血清ATP、IL-1β、IL-18、肿瘤坏死因子α(TNF-α)、抗Ⅱ型胶原抗体亚型(anti-ColⅡ-IgG、anti-ColⅡ-IgG2a)水平均降低,同时DC表面CD39分子表达量升高(P<0.05)。H&E染色显示,rmIL-37b 10μg/kg组大鼠关节损伤明显减轻。结论rmIL-37b可通过上调DC表面CD39分子表达,促进ATP水解,进而抑制滑膜组织中NLRP3炎症小体及炎症因子的表达,达到减轻RA模型大鼠关节炎症的目的。
To discuss the effect of interleukin-37b(IL-37b)on the inflammation in rheumatoid arthritis(RA)rats by regulating dendritic cells(DC)CD39/ATP axis.SD rats were recruited and randomly divided into normal control group,CIA model group,rmIL-37b 5µg/kg and rmIL-37b 10µg/kg group,with 10 rats in each group.Except control group,other rats were injected subcutaneously with collagen at the base of the tail to establish CIA model.At the day when the CIA model was confirmed,rmIL-37b group was injected with 5µg/kg or 10µg/kg rmIL37b respectively,while CTL group and CIA model group were injected with the same volume of(1 ml/kg)normal saline for 15 days.The pathological change of joint tissue was examined by H&E;IHC was used to detect the NODlike receptor pyrin domain containing 3(NLRP3)inflammasome in synovial tissues;DC phenotypes was detected by FCM;the ATP,cytokines and anti-ColⅡlevels were analyzed by Kit assays.Compared with CIA model group,rmIL-37b 10µg/kg group demonstrated lower levels of the paw volume,arthritis index(AI),NLRP3 inflammasome,serum ATP,IL-1β,IL-18,tumor necrosis factorα(TNF-α),anti-ColⅡ-IgG,anti-ColⅡ-IgG2a,while higher level of CD39 on the surface of DC(P<0.05).H&E staining showed that the joint injury of mice with rmIL-37b treatment was significantly reduced.In conclusion,rmIL-37b would release the rheumatoid arthritis by up-regulating CD39 on the DC surface,inducing ATP hydrolysis,and inhibiting NLRP3 inflammasome and cytokines expressions.
作者
李树岗
贾超
宋远瑛
LI Shugang;JIA Chao;SONG Yuanying(Department of Rheumatology and Immunology,Wuhan No.1 Hospital,Wuhan 430000,China;Department of Rheumatology,Hubei Provincial Hospital of Traditional Chinese Medicine,Wuhan 430061,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2022年第1期51-58,共8页
Immunological Journal
