高迁移率族蛋白B1对树突状细胞表型、吞噬功能及ERK/JNK/P38 MAPK信号通路的影响  

Effects of HMGB1 on phenotypes,phagocytosis and ERK/JNK/P38 MAPK signaling pathway in dendritic cells

作　　者：陈颖颖[1,2] 陈兰 牟志向 胡小龙 张艺艳 翁娇青 吕佩瑜 关天俊[1,2] CHEN Ying-ying;CHEN Lan;MOU Zhi-xiang;HU Xiao-long;ZHANG Yi-yan;WENG Jiao-qing;LYU Pei-yu;GUAN Tian-jun(Dept of Nephrology,Zhongshan Hospital Affiliated to Xiamen University,Xiamen Fujian 361004,China;Xiamen Hemodialysis Quality Control Center,Xiamen Fujian 361004,China;Division of Medical Affairs,Xiamen Healthcare Commission,Xiamen Fujian 361004,China;Dept of Pharmacy,Zhongshan Hospital Affiliated to Xiamen University,Xiamen Fujian 361004,China)

机构地区：[1]厦门大学附属中山医院肾内科,福建厦门361004 [2]厦门市血液透析质量控制中心,福建厦门361004 [3]厦门市卫生健康委员会医政处,福建厦门361004 [4]厦门大学附属中山医院药学部,福建厦门361004

出　　处：《中国药理学通报》2024年第2期248-255,共8页Chinese Pharmacological Bulletin

基　　金：福建省自然科学基金计划项目(No 2021J05281)。

摘　　要：目的探究高迁移率族蛋白B1(high mobility group box 1,HMGB1)对硫酸吲哚酚(indoxyl sulfate,IS)诱导的树突状细胞(DCs)表型、吞噬功能及细胞外信号调节激酶(ERK)/氨基末端蛋白激酶(JNK)/丝裂原活化蛋白激酶P38抗体(P38 MAPK)信号通路的影响。方法分别以30、300、600μmol·L^(-1)IS干预人原代DC细胞24 h,分为Control组、IS-30组、IS-300组、IS-600组,通过流式细胞分析鉴定细胞表型并检测细胞吞噬功能;细胞经600μmol·L^(-1)IS干预24 h后加入1 mg·L^(-1)anti-HMGB1或经1 mg·L^(-1)HMGB1单独处理后分为Control组、IS组、HMGB1组、IS^(+)anti-HMGB1组,通过流式细胞分析鉴定细胞表型并检测细胞吞噬功能;Western blot和免疫荧光染色检测ERK/JNK/P38 MAPK信号通路相关蛋白表达。结果随IS浓度增加,CD83^(+)和CD86^(+)细胞数逐渐增加(P<0.01),DCs吞噬能力逐渐下降(P<0.01);与IS组相比,IS^(+)anti-HMGB1组的CD83^(+)和CD86^(+)细胞数明显减少(P<0.01),细胞吞噬能力增加(P<0.01)。此外,与Control组比较,IS或HMGB1组p-ERK/ERK、p-P38/P38、p-JNK/JNK的蛋白表达升高(均P<0.01);与IS组相比,IS^(+)anti-HMGB1组p-ERK/ERK、p-p38/p38、p-JNK/JNK的蛋白表达降低(均P<0.01)。结论拮抗HMGB1可抑制IS诱导的DCs表型及成熟并抑制ERK/JNK/P38 MAPK信号通路激活。Aim To explore the impacts of high mobility group box 1(HMGB1)on the phenotypes,endocytosis and extracellular signal-regulated kinase(ERK)/Jun N-terminal protein kinase(JNK)/P38 mitogen-activated protein kinase(MAPK)signaling pathway in indoxyl sulfate(IS)-induced dendritic cells(DCs).Methods After treatment with 30,300 and 600μmol·L^(-1)IS for 24 h,human primary DCs were classified into control,IS-30,IS-300 and IS-600 groups.Flow cytometry was used to identify the phenotypes of DCs and detect phagocytosis.After single treatment with 1 mg·L^(-1)HMGB1,or 24 h of pretreatment with 600μmol·L^(-1)IS followed by exposure to 1 mg·L^(-1)anti-HMGB1,cells were classified into control,IS,HMGB1 and IS+anti-HMGB1 groups.The flow cytometry was again used to identify the phenotypes of DCs and detect phagocytosis.Western blot and immunofluorescence staining were used to analyze the expressions of ERK/JNK/P38 MAPK signaling-associated proteins.Results The number of CD83+and CD86+cells was elevated(P<0.01)and the phagocytotic ability of cells declined(P<0.01)with the increasing concentrations of IS.Relative to the IS group,the number of CD83+-and CD86+-positive cells declined(P<0.01)and the phagocytotic ability of cells was enhanced(P<0.01)in the IS+anti-HMGB1 group.Additionally,by contrast with the control group,p-ERK/ERK,p-P38/P38,p-JNK/JNK expressions were all raised in the IS group or HMGB1 group(all P<0.01).The p-ERK/ERK,p-p38/p38,p-JNK/JNK expressions all decreased in the IS+anti-HMGB1 group compared with the IS group(all P<0.01).Conclusion HMGB1 antagonist might suppress DCs phenotypes and maturation as well as block the activation of ERK/JNK/P38 MAPK signaling upon exposure to IS.

关 键 词：高迁移率族蛋白B1 树突状细胞 硫酸吲哚酚 表型 吞噬功能 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R341[医药卫生—基础医学] R345.57R392.11R692