Apoptosis最新文献

{"title":"Intravenous immunoglobulin ameliorates doxorubicin-induced intestinal mucositis by inhibiting the Syk/PI3K/Akt axis and ferroptosis","authors":"Xiaochen Yan,&nbsp;Peng Jiang,&nbsp;Changqing Li,&nbsp;Fengjuan Liu,&nbsp;Ping Fu,&nbsp;Dengqun Liu,&nbsp;Xi Du,&nbsp;Li Ma,&nbsp;Tong Wang,&nbsp;Xin Yuan,&nbsp;Shengliang Ye,&nbsp;Zongkui Wang","doi":"10.1007/s10495-024-02064-y","DOIUrl":"10.1007/s10495-024-02064-y","url":null,"abstract":"<div><h3>Background</h3><p>Chemotherapy-induced mucositis (CIM) significantly impacts quality of life and reduces survival in patients treated with specific chemotherapeutic agents. However, effective clinical treatments for CIM remain limited. Intravenous immunoglobulin (IVIg), a therapeutic derived from pooled human plasma, is widely used to treat inflammatory diseases. This study aimed to evaluate the therapeutic efficacy and underlying mechanisms of IVIg in CIM.</p><h3>Methods</h3><p>A murine model of doxorubicin (Dox)-induced intestinal mucositis and an organoid model of small intestinal injury were used to explore the protective effects of IVIg on CIM. Immunostaining, transmission electron microscopy (TEM), western blotting (WB), and proteomic analysis were used to further investigate ferroptosis in intestinal epithelial cells and the underlying mechanisms.</p><h3>Results</h3><p>In the murine model of Dox-induced intestinal mucositis, intestinal epithelial barrier was destroyed and ferroptosis increased, characterized by weight loss, hematological injury, inflammation, mitochondrial atrophy in intestinal epithelial cells, lipid peroxidation, impairment of tight junctions, and damage to intestinal microvilli. IVIg treatment significantly ameliorated intestinal epithelial barrier damage and reduced ferroptosis both in vitro and in vivo. Proteomic analysis revealed that the FcγR-mediated phagocytosis signaling pathway was involved in the therapeutic effects of IVIg on CIM mice. WB results demonstrated that key proteins downstream of this pathway, Syk, PI3K, and Akt, showed increased phosphorylation in CIM mice, whereas IVIg treatment significantly reduced the phosphorylation levels. Furthermore, the inhibitory effects of IVIg on Dox-induced activation of the Syk/PI3K/Akt axis and ferroptosis, as well as its protective effects on intestinal inflammation and intestinal barrier damage, were reversed by 740Y-P (an PI3K activator) or SC79 (an Akt activator).</p><h3>Conclusions</h3><p>Our findings highlight that IVIg ameliorates CIM by inhibiting ferroptosis via the Syk/PI3K/Akt axis. These results suggest that IVIg may represent a potential therapeutic approach for CIM.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"734 - 750"},"PeriodicalIF":6.1,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-02064-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PWP1 transcriptionally regulates p53, modulating apoptosis and cell cycle to promote gastric cancer progression","authors":"Mingrui Jiang,&nbsp;Sen Wang,&nbsp;Jin Ji,&nbsp;Shantanu Baral,&nbsp;Qiannan Sun,&nbsp;Yong Wang,&nbsp;Bin Liu,&nbsp;Jun Ren,&nbsp;Wei Wang,&nbsp;Daorong Wang","doi":"10.1007/s10495-024-02049-x","DOIUrl":"10.1007/s10495-024-02049-x","url":null,"abstract":"<div><p>Gastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis often depends on early detection and understanding the molecular mechanisms involved in its progression. Periodic tryptophan protein 1 (PWP1) has emerged as a novel diagnostic marker, potentially linked to gastric cancer progression. This study aims to elucidate the impact of PWP1 on gastric cancer development, focusing on apoptosis, cell cycle regulation, and the role of p53. This study utilized gastric cancer cell lines to investigate the expression and functional role of Pwp1. Quantitative PCR and Western blot analyses were conducted to measure PWP1 expression levels. Apoptosis was assessed by using flow cytometry and TUNEL assays, and cell cycle analysis was performed to evaluate the impact of PWP1 modulation. Additionally, animal experiments were conducted using mouse models injected with gastric cancer cells, with PWP1 knockdown or overexpression, to observe tumor growth and progression. Statistical significance was evaluated using t-tests and ANOVA where appropriate. Elevated PWP1 expression was observed in gastric cancer tissues compared to normal tissues. PWP1's knockdown resulted in increased apoptosis and cell cycle arrest at the G1 phase, suggesting its role in promoting invasion and proliferation. Furthermore, animal experiments demonstrated reduced tumor growth in mice with PWP1 knockdown. PWP1 was found to transcriptionally regulate p53, affecting its expression and thereby influencing apoptosis and cell cycle pathways in gastric cancer. Our study identifies PWP1 as a novel oncogene frequently overexpressed in gastric cancer (GC). Through transcriptional regulation of p53, PWP1 enhances cell growth by influencing apoptosis and inducing G1 phase cell cycle arrest. These findings underscore PWP1 as a promising therapeutic target for treating GC, suggesting its potential for future clinical applications.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"693 - 709"},"PeriodicalIF":6.1,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-02049-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM23 promotes 5-Fluorouracil resistance in colorectal cancer by upregulating GALNT4 expression","authors":"Shanshan Wei,&nbsp;Wei Xia,&nbsp;Jun Feng,&nbsp;Jianwen Lu,&nbsp;Luo Zhang,&nbsp;Wei Wang,&nbsp;Wenwei Hu,&nbsp;Yiting Geng","doi":"10.1007/s10495-024-02060-2","DOIUrl":"10.1007/s10495-024-02060-2","url":null,"abstract":"<div><p>5-Fluorouracil (5-FU) is one of the most common chemotherapeutic agents for colorectal cancer (CRC), but its application is often limited by resistance. Tripartite motif containing 23 (TRIM23) has been reported to be dysregulated in various tumors and involved in tumor progression and chemotherapy resistance. However, its relationship with CRC 5-FU resistance and the underlying mechanism are still unclear. In this study, we found that TRIM23 was upregulated in CRC. Patients treated with 5-FU and with high TRIM23 expression had a lower disease control rate (DCR) and a poorer median progression-free survival (mPFS). In vitro, the expression of TRIM23 in CRC cells was elevated after 5-FU treatment. Compared to parental cells, TRIM23 was significantly overexpressed in 5-FU-resistant CRC cells. Mechanistically, TRIM23 mediated 5-FU resistance of CRC by upregulating the expression of N-acetylgalactosaminyltransferase-4 (GALNT4). Knocking down TRIM23 in 5-FU-resistant colon cancer cells restored the sensitivity to 5-FU, while overexpression of GALNT4 in TRIM23 knockdown cells counteracted the chemosensitization caused by TRIM23 downregulation. The TRIM23/GALNT4 axis may play a crucial role in 5-FU resistance in CRC, and targeted inhibition of this axis is expected to reverse resistance. As a potential biomarker for screening 5-FU-sensitive patients and predicting prognosis in clinical practice, TRIM23 deserves further investigation.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"751 - 767"},"PeriodicalIF":6.1,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-02060-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of copper in cell death and cancer","authors":"Jiahao Xie,&nbsp;Yue Su,&nbsp;Wenzhong Shang,&nbsp;Yanfang Wu,&nbsp;Junjia He,&nbsp;Ting Li,&nbsp;Yeyu Shen,&nbsp;Youni Zhang,&nbsp;Xiangmin Tong,&nbsp;Qiong Bian","doi":"10.1007/s10495-024-02059-9","DOIUrl":"10.1007/s10495-024-02059-9","url":null,"abstract":"<div><p>Copper (cu) is an essential micronutrient required for numerous metabolic processes. It plays a crucial role in cellular respiration by participating in the electron transport chain and facilitating numerous biological reactions. Various diseases, including cancer, demonstrate localized elevation of copper levels and/or alterations in the overall distribution of copper. Modulating local or systemic copper levels as a novel therapeutic approach for treating and ameliorating diseases has emerged as a prominent trend in disease management, particularly in the realm of cancer therapy, which is currently under investigation. The objective of this review is to offer a thorough examination of copper metabolism in both physiological and pathological contexts. Specifically, it delves into how copper ions can effectively target and stimulate tumor cell death via the process known as cuproptosis in cancer patients. Furthermore, this review explores the utilization of three categories of anticancer medications (copper ion carriers, copper complexes, and copper chelating agents) pertaining to copper metabolism within the realm of cancer therapy, elucidating on the distinct mechanisms through which they exert their effects.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 1-2","pages":"488 - 505"},"PeriodicalIF":6.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Necroptosis in obesity: a complex cell death event","authors":"Zunhai Liu,&nbsp;Simeng Wang,&nbsp;Wentao Wang,&nbsp;Rui Lv,&nbsp;Chao Sun","doi":"10.1007/s10495-024-02055-z","DOIUrl":"10.1007/s10495-024-02055-z","url":null,"abstract":"<div><p>Obesity is an exceedingly prevalent and frequent health issue in today’s society. Fat deposition is accompanied by low-grade inflammation in fat tissue and throughout the body, leading to metabolic disorders that ultimately promote the onset of obesity-related diseases. The development of obesity is accompanied by cell death events such as apoptosis as well as pyroptosis, however, the role of necroptosis in obesity has been widely reported in recent years. Necroptosis, a mode of cell death distinct from apoptosis and necrosis, is associated with developing many inflammatory conditions and their associated diseases. It also exhibits modulation of apoptosis and pyroptosis. It is morphologically similar to necroptosis, characterized by the inhibition of caspase-8, the formation of membrane pores, and the subsequent rupture of the plasma membrane. This paper focuses on the key pathways and molecules of necroptosis, exploring its connections with apoptosis and pyroptosis, and its implications in obesity. This paper posits that the modulation of necroptosis-related targets may represent a novel potential therapeutic avenue for the prevention and treatment of obesity-induced systemic inflammatory responses, and provides a synopsis of potential molecular targets that may prove beneficial in obesity-associated inflammatory diseases.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 1-2","pages":"466 - 487"},"PeriodicalIF":6.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EFNA4-enhanced deubiquitination of SLC7A11 inhibits ferroptosis in hepatocellular carcinoma","authors":"Xingyi Zhong,&nbsp;Zhiqin Zhu,&nbsp;Yangfeng Du,&nbsp;Lingzhi Long,&nbsp;Ziping Xie,&nbsp;Yangfeng Zhang,&nbsp;Huijun Yao,&nbsp;Junhao Lin,&nbsp;Fengsheng Chen","doi":"10.1007/s10495-024-02042-4","DOIUrl":"10.1007/s10495-024-02042-4","url":null,"abstract":"<div><p>EFNA4, a member of the Ephrin-A ligand family, may influence hepatocellular carcinoma cells through two distinct mechanisms: one reliant on specific Eph receptor binding and the other independent of receptor involvement. However, EFNA4's influence on HCC via non-Eph receptor pathways remains unclear. In this study, we aimed to investigate the role of EFNA4 in a receptor-independent environment. Firstly, we constructed an environment lacking Eph receptors via CRISPR/Cas9 and found that EFNA4 could still partially promote HCC proliferation and metastasis in vivo and in vitro. Further analyses of apoptosis, ROS, and GPX4 expression revealed that overexpression of EFNA4 would inhibit ferroptosis in HCC. Mechanistically, EFNA4 was positively correlated with SLC7A11 and directly interacted with SLC7A11 in HCC via bioinformatics analysis. We demonstrated that the structural domain (a.a. 161–201) of EFNA4 specifically binds to the domain (a.a. 222–501) of SLC7A11, which led to the deubiquitination of SLC7A11. Subsequently, we found that EFNA4 would recruit the deubiquitinase USP9X, resulting in inhibition of SLC7A11 degradation, which ultimately inhibits ferroptosis and enhances the proliferation and metastasis of HCC. In conclusion, we demonstrated that EFNA4 promotes the proliferation and metastasis of HCC independent of Eph receptors by inhibiting ferroptosis and advancing the deubiquitination of SLC7A11 by recruiting the deubiquitinase USP9X. This indicates that EFNA4 could act as a potential prognostic marker and a prospective therapeutic target in patients with HCC.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 1-2","pages":"349 - 363"},"PeriodicalIF":6.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-02042-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia programmed cell death in neurodegenerative diseases and CNS injury","authors":"Ling Cai,&nbsp;Qiuyue Fan,&nbsp;Rui Pang,&nbsp;Chen Chen,&nbsp;Yueman Zhang,&nbsp;Haiyi Xie,&nbsp;Jingyi Huang,&nbsp;Yu Wang,&nbsp;Peiying Li,&nbsp;Dan Huang,&nbsp;Xia Jin,&nbsp;Yuxi Zhou,&nbsp;Yan Li","doi":"10.1007/s10495-024-02041-5","DOIUrl":"10.1007/s10495-024-02041-5","url":null,"abstract":"<div><p>Programmed cell death (PCD) has emerged as a critical regulatory mechanism in the initiation and progression of various pathological conditions. PCD in microglia, including necroptosis, pyroptosis, apoptosis, ferroptosis, and autophagy, occurs in a variety of central nervous system (CNS) diseases. Dysregulation of microglia can lead to excessive tissue damage or neuronal death in CNS injury. Various injury stimuli trigger aberrant activation of the PCD pathway of microglia, which then further leads to inflammatory cascades that exacerbates CNS pathology in a vicious cycle. Therefore, targeting PCD in microglia is considered an important avenue for the treatment of various neurodegenerative diseases and CNS injury. In this review, we summarize the major and recent findings focusing on the mechanisms of PCD in microglia modulating functions in neurodegenerative diseases and CNS injury and provide a systematic overview of the current inhibitors targeting various PCD pathways, which may provide important therapeutic targets that merit further investigation.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 1-2","pages":"446 - 465"},"PeriodicalIF":6.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-02041-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial CLPB is a pro-survival factor at the onset of granulocytic differentiation of mouse myeloblastic cells","authors":"Tomasz Wenta,&nbsp;Guanpeng Wang,&nbsp;Tessa Van Buren,&nbsp;Michal Zolkiewski,&nbsp;Anna Zolkiewska","doi":"10.1007/s10495-024-02053-1","DOIUrl":"10.1007/s10495-024-02053-1","url":null,"abstract":"<div><p>Loss-of-function mutations in the <i>CLPB</i> gene lead to congenital neutropenia due to impaired neutrophil differentiation. CLPB, a member of the AAA+ family of proteins, resides in the intermembrane space of mitochondria. The mechanism by which a loss of CLPB elicits defects in the differentiation program of neutrophil precursor cells is not understood. Here, we used 32D clone 3 (32Dcl3) cells, an interleukin-3 (IL-3)-dependent mouse myeloblastic cell line model, to investigate the effects of CLPB knockout on myeloblast-to-neutrophil differentiation in vitro. We found that CLPB-deficient 32Dcl3 cells showed a decreased mitochondrial membrane potential and increased levels of insoluble HAX1 aggregates in mitochondria, as compared to control cells. Despite those abnormalities, CLPB loss did not affect cell proliferation rates in the presence of IL-3 but it increased apoptosis after IL-3 withdrawal and simultaneous induction of cell differentiation with granulocytic colony stimulating factor (G-CSF). CLPB-deficient cells that survived the stress associated with IL-3 withdrawal/G-CSF treatment expressed the same levels of differentiation markers as control cells. Moreover, we found that increased apoptosis of CLPB-deficient cells is linked to production of reactive oxygen species (ROS). <i>N</i>-acetylcysteine, exogenous free fatty acids, or exogenous citrate protected CLPB-deficient 32Dcl3 cells from apoptosis at the onset of differentiation. The protective effect of citrate was abolished by inhibition of ATP-citrate lyase (ACLY), an enzyme that converts cytosolic citrate into acetyl-CoA, a substrate for protein acetylation. We propose that citrate supplementation may help mitigate the effects of CLPB loss by facilitating ACLY-dependent ROS detoxification in granulocytic precursor cells.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 1-2","pages":"334 - 348"},"PeriodicalIF":6.1,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GAS5 long non-coding RNA interacts with microRNA-205 to relieve fibroblast-like synoviocyte inflammation and ferroptosis in osteoarthritis","authors":"Yanglin Gu,&nbsp;Guangchang Wang,&nbsp;Peng Chen","doi":"10.1007/s10495-024-02051-3","DOIUrl":"10.1007/s10495-024-02051-3","url":null,"abstract":"<div><p>This study aimed to explore the role of the growth arrest-specific five gene (<i>GAS5</i>) long non-coding RNA (lncRNA) in fibroblast-like synoviocytes (FLSs) during the development of osteoarthritis (OA). A total of 25 OA synovial tissues and nine healthy control tissues were collected, and their GAS5 expression was compared. To confirm GAS5 expression in vitro, interleukin (IL)-1β was used to mimic a cellular OA model based on isolated FLSs. Quantitative polymerase chain reaction revealed higher expression levels of <i>GAS5</i> in OA samples than in non-OA samples. In vitro, the stimulation of FLSs by IL-1β induced high <i>GAS5</i> expression. The IL-1β-exposed cells exhibited impaired growth, viability, and antioxidant capacity, as well as increased cell death, production of cellular and lipid ROS, and inflammatory cytokine levels. The expression levels of ferroptosis-related proteins in FLSs were also altered in IL-1β-exposed cells. <i>GAS5</i> was observed to directly target and inhibit micro-RNA 205, partially reversing the effect of <i>GAS5</i> silencing on cell proliferation, cell death, oxidative stress, inflammation, and FLS ferroptosis. FLS ferroptosis is recognized to be involved in OA development, and the downregulation of the GAS5 lncRNA exhibits protective effects by suppressing ferroptosis and sponging miR-205 in FLSs in OA, thereby providing a novel strategy for the treatment of OA. The <i>GAS5</i>–miR–205 axis can regulate inflammation and oxidative stress in the FLSs of patients with OA.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 1-2","pages":"320 - 333"},"PeriodicalIF":6.1,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotic DNA regulates intestinal Th2 polarization by inducing epithelial cells to produce PD-L1","authors":"Shuo Song,&nbsp;Hanqing Zhang,&nbsp;Le Liu,&nbsp;Minyao Li,&nbsp;Xiangyu Wang,&nbsp;Haotao Zeng,&nbsp;Miao Zhao,&nbsp;Pixin Ran,&nbsp;Qing Shu,&nbsp;Pingchang Yang","doi":"10.1007/s10495-024-02043-3","DOIUrl":"10.1007/s10495-024-02043-3","url":null,"abstract":"<div><p>Th2 polarization is a characteristic feature of many immune diseases; its pathogenesis is still being elucidated. Probiotics have immune regulatory effects. This study is aimed at testing the impact of <i>Lactobacillus rhamnosus</i> (LR) DNA on regulating Th2 polarization and elucidating its underlying mechanism. In this study, ovalbumin plus alum protocol was used to establish the Th2 polarization status in the mouse intestine. Mice received LR-DNA gavage daily for five days. The expression of programmed cell death ligand-1 (PD-L1) in intestinal epithelial cells was assessed using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. The results showed that the expression of PD-L1 was detected in mouse intestinal epithelial cells, which was up regulated by LR-DNA gavage daily for 5 days. The expression of PD-L1 was also detected in T84 cells, which could be increased by exposing them to LR-DNA in culture. RNA sequencing results showed that the gene activities of <i>Kdm5a</i>, <i>foxo1</i> and <i>Pdl1</i> could be upregulated by LR-DNA in mouse intestinal epithelial cells. The epithelial cell-derived PD-L1 induced the activated Th2 cell apoptosis by interacting with programmed cell death protein-1 (PD-1). Administration of LR-DNA, but not live probiotics, alleviated experimental Th2 polarization in a food allergy mouse model. In conclusion, LR-DNA induces intestinal epithelial cells to produce PD-L1, which induces the activated Th2 cell apoptosis. Administration of LR-DNA mitigated experimental Th2 polarization in the intestine.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 1-2","pages":"239 - 249"},"PeriodicalIF":6.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}