收稿日期: 2023-02-06
网络出版日期: 2023-09-26
基金资助
四川省科技计划项目(2023JDRC0109);四川省科技计划资助(2022YFS0631);西南医科大学校级基金(2018-ZRQN-024)
Role of peroxisome proliferator⁃activated receptors⁃γ in modulating P. acnes⁃induced pyroptosis， cell proliferation and apoptosis in human keratinocytes
Received date: 2023-02-06
Online published: 2023-09-26
目的 分析过氧化物酶体增殖物激活受体-γ（peroxisome proliferator-activated receptors， 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。
易莎 , 胡楠 , 李粤 , 杨林 , 张玉婷 , 熊霞 , 钟桂书 , 陈燕 . 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[J]. 实用医学杂志, 2023 , 39(16) : 2043 -2049 . DOI: 10.3969/j.issn.1006-5725.2023.16.006
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-γ in acne and normal skin tissues were evaluated using IHC. By lentiviral transfection， PPAR-γ was upregulated in HaCaT cells， and the expression of PPAR-γ was verified by Western blot. ELISA was performed to analyze the levels of P. acnes-induced pyroptotic-associated inflammatory factors IL-1β and 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-γ expression． Results PPAR-γ expression was significantly decreased in acne （P < 0.05）. Compared with the control， the P. acnes-induced pyroptotic-associated inflammatory factors IL-1β and 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-γ reduced the expression of IL-1β and 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-γ can effectively regulate P. acnes-induced pyroptosis， cell proliferation and apoptosis in human keratinocytes.
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