Yi Chengxue, Wang Haoyu, Din Muhammad Azhar Ud, Xia Yuxuan, Akanyibah Francis Atim, Mao Fei
School of Medical Technology, Zhenjiang College Zhenjiang 212028, Jiangsu, P. R. China.
Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, P. R. China.
Am J Transl Res. 2024 Nov 15;16(11):6903-6913. doi: 10.62347/PKYU4876. eCollection 2024.
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.
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 α (TNF-α), and interleukins (IL)-1β, 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.
HucMSC-Ex treatment significantly reduced the expression of pro-inflammatory cytokines, such as TNF-α, IL-1β, 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.
Our results support that hucMSC-Ex alleviates LPS-induced cervical inflammation, possibly by inhibition of EMT.
已知慢性宫颈炎患者感染人乳头瘤病毒（HPV）的风险增加，而HPV是宫颈癌的主要病因。抑制宫颈炎症可能降低患宫颈癌的风险。本研究探讨了人脐带间充质干细胞来源的外泌体（hucMSC-Ex）如何减轻脂多糖（LPS）诱导的宫颈炎症。
用人子宫鳞状癌细胞（SiHa）用LPS诱导构建炎症模型，并用hucMSC-Ex处理。通过qRT-PCR分析肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1β、IL-6、IL-10的表达水平。采用蛋白质免疫印迹法检测细胞中环氧合酶-2（COX-2）和增殖细胞核抗原（PCNA）的蛋白表达水平，并用CCK8检测细胞增殖，以探讨hucMSC-Ex对细胞炎症的缓解作用。还通过qRT-PCR和蛋白质免疫印迹法评估SiHa细胞中上皮-间质转化（EMT）标志物的表达，以确定hucMSC-Ex对炎症的影响。此外，收集临床宫颈涂片，通过免疫荧光检测临床脱落细胞样本中EMT标志物的表达。
hucMSC-Ex处理显著降低了LPS诱导的炎症模型中促炎细胞因子如TNF-α、IL-1β和IL-6的表达，同时增加了包括IL-10在内的抗炎细胞因子水平，以减轻炎症。hucMSC-Ex增加了上皮标志物（如E-钙黏蛋白）的表达水平，同时降低了间质标志物（如N-钙黏蛋白）的表达，表明其抑制EMT。
我们的结果支持hucMSC-Ex减轻LPS诱导的宫颈炎症，可能是通过抑制EMT实现的。
