CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Human umbilical cord mesenchymal stem cells derived-exosomes alleviate LPS-induced cervical inflammation and epithelial-mesenchymal transition.
我们的结果支持 hucMSC-Ex 可减轻 LPS 诱导的宫颈炎症,其机制可能是通过抑制 EMT。
目的:慢性宫颈炎患者感染人乳头瘤病毒(HPV)的风险已知较高,HPV是宫颈癌的主要病因。抑制宫颈炎症可能降低宫颈癌风险。本研究探讨人脐带间充质干细胞来源外泌体(hucMSC-Ex)如何减轻脂多糖(LPS)诱导的宫颈炎症。 方法:使用LPS刺激人宫颈鳞状细胞癌SiHa细胞建立炎症模型,并给予hucMSC-Ex处理。通过qRT-PCR分析肿瘤坏死因子(TNF-α)及白细胞介素(IL)-1β、IL-6和IL-10的表达;使用蛋白质印迹检测细胞中环氧合酶2(COX-2)和增殖细胞核抗原(PCNA)蛋白表达,并通过CCK8检测细胞增殖,以探究hucMSC-Ex对细胞炎症的缓解作用。还通过qRT-PCR和蛋白质印迹分析SiHa细胞上皮-间质转化(EMT)标志物表达,以评估hucMSC-Ex对炎症的作用。此外,采集临床宫颈涂片,通过免疫荧光检测临床脱落细胞样本中的EMT标志物表达。 结果:hucMSC-Ex处理显著降低LPS诱导炎症模型中TNF-α、IL-1β和IL-6等促炎细胞因子的表达,同时提高抗炎细胞因子IL-10水平,从而减轻炎症。hucMSC-Ex上调上皮标志物(如E-cadherin)表达,同时下调间质标志物(如N-cadherin)表达,提示其可抑制EMT。 结论:结果支持hucMSC-Ex可缓解LPS诱导的宫颈炎症,可能通过抑制EMT发挥作用。
OBJECTIVE: Patients with chronic cervicitis are known to have an increased risk of infection with human papillomavirus (HPV), which is the primary cause of cervical cancer. Inhibition of cervical inflammation may reduce the risk of cervical cancer. This study investigated how human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) attenuated the lipopolysaccharide (LPS)-induced cervical inflammation. METHODS: Human uterine squamous carcinoma (SiHa) cells were induced with LPS to construct an inflammatory model and treated with hucMSC-Ex. The expression levels of tumor necrosis factor (TNF- ), and interleukins (IL)-1 , IL-6, IL-10 were analyzed by qRT-PCR. Western blot was used to detect the protein expression levels of cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) in cells, and CCK8 was used to examine cell proliferation, so as to explore the relieving effect of hucMSC-Ex on cell inflammation. The expression of epithelial-mesenchymal transition (EMT) markers in SiHa cells was also assessed by qRT-PCR and western blot to determine the effect of hucMSC-Ex on inflammation. Moreover, clinical cervical smears were collected to detect the expression of EMT markers in clinical exfoliated cell samples by immunofluorescence. RESULTS: HucMSC-Ex treatment significantly reduced the expression of pro-inflammatory cytokines, such as TNF- , IL-1 , and IL-6 in the LPS-induced inflammation model, while increasing the level of anti-inflammatory cytokines, including IL-10, to reduce inflammation. HucMSC-Ex increased the expression level of epithelial markers (such as E-cadherin) while it decreased the expression of interstitial markers (such as N-cadherin), suggesting it inhibits EMT. CONCLUSIONS: Our results support that hucMSC-Ex alleviates LPS-induced cervical inflammation, possibly by inhibition of EMT.
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