过氧化物酶体增殖物激活受体-γ对P.acnes诱导的人角质形成细胞焦亡、增殖及凋亡的影响  

Role of peroxisome proliferator⁃activated receptors⁃γin modulating P.acnes⁃induced pyroptosis,cell pro⁃liferation and apoptosis in human keratinocytes

作　　者：易莎 胡楠 李粤 杨林 张玉婷 熊霞 钟桂书 陈燕 YI Sha;HU Nan;LI Yue;YANG Lin;ZHANG Yuting;XIONG Xia;ZHONG Guishu;CHEN Yan(Department of Dermatology,The Affiliated Hospital,Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学附属医院皮肤科,四川泸州646000

出　　处：《实用医学杂志》2023年第16期2043-2049,共7页The Journal of Practical Medicine

基　　金：四川省科技计划项目(编号:2023JDRC0109);四川省科技计划资助(编号:2022YFS0631);西南医科大学校级基金(编号:2018-ZRQN-024,2020ZRZD001)。

摘　　要：目的分析过氧化物酶体增殖物激活受体-γ(peroxisomeproliferator-activatedreceptors,PPAR-γ)对痤疮丙酸杆菌Propionibacterium acnes(P.acnes)诱导的细胞焦亡、增殖及凋亡效应的影响,为痤疮的临床治疗提供新的理论依据。方法采用IHC方法检测痤疮患者皮损中PPAR-γ的表达。使用慢病毒转染,在HaCaT细胞中过表达PPAR-γ,1×107 CFU/mL P.acnes诱导细胞,通过Western blot验证PPAR-γ蛋白的表达;采用ELISA法检测细胞内焦亡相关炎症因子IL-1β和IL-18;EdU和流式细胞术检测细胞增殖和凋亡;Western blot检测细胞焦亡相关蛋白,如NOD样受体家族3(NLRP3)蛋白、活化的半胱天冬酶1(Caspase-1)、Gasdermin D(GSDMD)的表达水平。结果PPAR-γ在痤疮组织中表达明显降低(P<0.05)。与对照组相比,P.acnes处理后,细胞焦亡相关炎症因子IL-1β和IL-18增加(P<0.01);细胞焦亡相关蛋白NLRP3、Caspase-1和GSDMD的表达水平增加(P<0.05)。过表达PPAR-γ后,在P.acnes诱导下,过表达组与对照组比IL-1β和IL-18明显降低,细胞增殖能力增加,凋亡水平明显下降,细胞焦亡相关蛋白NLRP3、Caspase-1和GSDMD的表达减少,且差异均有统计学意义(P<0.05)。结论PPAR-γ可有效调节P.acnes诱导的细胞焦亡并对人角质形成细胞增殖、凋亡进行调控。Objective To analyze the role of peroxisome proliferator-activated receptors(PPAR-γ)expression in P.acnes-induced pyroptosis,cell proliferation and apoptosis in human keratinocytes(HaCaT)so as to provide a new theoretical basis for clinical treatment.Methods Expression patterns of PPAR-γin acne and normal skin tissues were evaluated using IHC.By lentiviral transfection,PPAR-γwas upregulated in HaCaT cells,and the expression of PPAR-γwas verified by Western blot.ELISA was performed to analyze the levels of P.acnesinduced pyroptotic-associated inflammatory factors IL-1βand IL-18.EdU assay and flow cytometry were used to detect the cell proliferation and apoptosis ability.Western blot was used to determine the levels of NLR family pyrin domain containing 3(NLRP3),cysteinyl aspartate specific proteinase-1(caspase-1),Gasdermin D(GSDMD)and PPAR-γexpression.Results PPAR-γexpression was significantly decreased in acne(P<0.05).Compared with the control,the P.acnes-induced pyroptotic-associated inflammatory factors IL-1βand IL-18 were increased(P<0.01),the pyroptotic-associated proteins were increased significantly(P<0.05).After treatment with P.acnes,the up-regulated PPAR-γreduced the expression of IL-1βand IL-18 and HaCaT cell apoptosis,promoted the cell proliferation,up-regulated the expression of NLRP3,Caspase-1 and GSDMD in human keratinocytes all in a statistically significant way(all P<0.05).Conclusion PPAR-γcan effectively regulate P.acnes-induced pyroptosis,cell proliferation and apoptosis in human keratinocytes.

关 键 词：过氧化物酶体增殖物激活受体-Γ 细胞焦亡 炎症因子 角质形成细胞 痤疮 细胞增殖 细胞凋亡 

分 类 号：R758.7[医药卫生—皮肤病学与性病学]