International immunopharmacology最新文献

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TLR4-mediated endoplasmic reticulum stress regulates pyroptosis in macrophages infected with the Bacillus Calmette-Guérin mycobacterial
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-09 DOI: 10.1016/j.intimp.2025.114346
Xueyi Nie , Shen'ao Miao , Yuxin Hou , Yabo Ma , Mengyuan Li , Yueyang Liu , Yi Yang , Jinrui Xu , Yujiong Wang
{"title":"TLR4-mediated endoplasmic reticulum stress regulates pyroptosis in macrophages infected with the Bacillus Calmette-Guérin mycobacterial","authors":"Xueyi Nie ,&nbsp;Shen'ao Miao ,&nbsp;Yuxin Hou ,&nbsp;Yabo Ma ,&nbsp;Mengyuan Li ,&nbsp;Yueyang Liu ,&nbsp;Yi Yang ,&nbsp;Jinrui Xu ,&nbsp;Yujiong Wang","doi":"10.1016/j.intimp.2025.114346","DOIUrl":"10.1016/j.intimp.2025.114346","url":null,"abstract":"<div><div>Tuberculosis results from <em>Mycobacterium tuberculosis</em> (Mtb) infection. Immune responses controlled by Toll-like receptor 4 (TLR4) are closely associated with the host response to pathogens, including Mtb. NLRP3 inflammasome-mediated pyroptosis forms a significant part of the inflammatory response during Mtb infection, and endoplasmic reticulum stress (ERS) is implicated in the activation of the NLRP3 inflammasome. Here, the function of TLR4 in macrophage pyroptosis induced by infection with the Bacillus Calmette-Guérin (BCG) mycobacterial strain was investigated. It was found that infection with BCG activated TLR4 signaling, induced ERS and subsequent NLRP3 inflammasome activation, leading to pyroptosis in mouse lung tissues. The TLR4 inhibitor TAK 242 inhibited the ERS onset, NLRP3 inflammasome stimulation, and pyroptosis, while the ERS inhibitor TUDCA blocked both inflammasome activation and pyroptosis, and the NLRP3 inhibitor MCC950 specifically inhibited pyroptosis. Furthermore, TAK 242, TUDCA, and MCC950 all exacerbated lung injury caused by BCG infection and promoted BCG survival. Similarly, after in BCG-infected THP-1 macrophages, TLR4 signaling was found to mediate NLRP3 inflammasome activation through ERS, thereby inducing pyroptosis. In summary, BCG infection leads to macrophage pyroptosis via the TLR4/ERS/NLRP3 inflammasome signaling axis, providing new insights for further research into the pathogenesis and treatment of tuberculosis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114346"},"PeriodicalIF":4.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Material basis and mechanism of Ephedra sinica in interfering with wind-chill cold
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-09 DOI: 10.1016/j.intimp.2025.114432
Yuanyuan Wu , Mengnan Zeng , Bing Cao , Beibei Zhang , Xiaoke Zheng , Weisheng Feng
{"title":"Material basis and mechanism of Ephedra sinica in interfering with wind-chill cold","authors":"Yuanyuan Wu ,&nbsp;Mengnan Zeng ,&nbsp;Bing Cao ,&nbsp;Beibei Zhang ,&nbsp;Xiaoke Zheng ,&nbsp;Weisheng Feng","doi":"10.1016/j.intimp.2025.114432","DOIUrl":"10.1016/j.intimp.2025.114432","url":null,"abstract":"<div><div><em>Ephedra sinica</em> has a long history in medicine, i.e., as the first medicinal plant for treating wind-chill colds. However, few studies have shown its material basis and mechanism of action, so this article mainly focuses on these two issues. Rats were stimulated by fan blowing and low temperature for 7 days, following which alkaloid extract (SWJ), non-alkaloid extract (FSWJ), and polysaccharide extract (DT) from <em>Ephedra sinica</em> (MH) were administered for 4 days. First, the body temperature, sweat spots, activity status, and cough-related indexes were detected to screen the pharmacodynamic material basis of MH. Then, the immune cells, ROS, MDA, GSH-PX, SOD, IL-4, IgE, TRPM8, TLR4, p-P65/P65, acetylcholine, and CHRM3 levels were detected to explore the potential mechanism of the SWJ. In addition, BEAS-2B cells were cultured at 26 °C for 12 h to establish a cell injury model induced by cold stimulation. BEAS-2B cells were co-cultured with spleen cells, and the effects of ephedrine (MHJ) and pseudoephedrine (WMHJ) on immune cells and inflammatory factors in this system were detected. The TRPM8 inhibitor (AMG-333) was added 3 h before administration to detect the effects of MHJ and WMHJ on the expression levels of TRPM8, TLR4, and P-P65/P65. Animal experiments showed that SWJ, FSWJ, and DT reduced body temperature and relieved symptoms such as sweating difficulty, listlessness, and cough, and SWJ produced the best effect. Subsequently, it was found that SWJ transformed immune cells, weakened oxidative stress, downregulated IL-4, IgE, TRPM8, TLR4, and P-P65/P65, and upregulated ACH and CHRM3. Cell experiments showed that MHJ and WMHJ upregulated the Ths and Tcs and downregulated IL-6, TNF-α, TRPM8, TLR4, and P-P65/P65. The intervention of AMG-333 affected the TRPM8 and p-P65/P65, but AMG-333 did not regulate TLR4. Taken together, alkaloid extract is the material basis for MH to improve rats' wind-chill cold and may protect rats from injury by regulating the TRPM8/TLR4-NFκB pathway and CHRM3, with ephedrine and pseudoephedrine possibly playing an important role.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114432"},"PeriodicalIF":4.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic evidence of methotrexate's protective role against Parkinson's disease: A Mendelian randomization and co-localization study
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-09 DOI: 10.1016/j.intimp.2025.114386
Fang-Shu Zou , Min-Ying Liu , Xiao-Na Ma , Mei-Feng Shi , Wei Feng , Qiang Xu
{"title":"Genetic evidence of methotrexate's protective role against Parkinson's disease: A Mendelian randomization and co-localization study","authors":"Fang-Shu Zou ,&nbsp;Min-Ying Liu ,&nbsp;Xiao-Na Ma ,&nbsp;Mei-Feng Shi ,&nbsp;Wei Feng ,&nbsp;Qiang Xu","doi":"10.1016/j.intimp.2025.114386","DOIUrl":"10.1016/j.intimp.2025.114386","url":null,"abstract":"<div><h3>Background</h3><div>Recent research has indicated a possible link between the use of methotrexate (MTX) and a heightened risk of developing Parkinson's disease (PD). Nevertheless, the causal relationship between MTX and PD continues to be unclear. This study aimed to explore the potential causal impact of MTX use on the risk of PD by employing two-sample Mendelian randomization (MR) alongside co-localization (COLOC) analysis.</div></div><div><h3>Objective</h3><div>The objective of this research is to explore the potential causal relationship between the use of methotrexate and the likelihood of developing Parkinson's disease, employing a two-sample Mendelian randomization (TSMR) methodology.</div></div><div><h3>Methods</h3><div>Separate datasets concerning the genetic tools associated with MTX and PD were acquired from the Genome-Wide Association Study (GWAS) database. A series of MR-related statistical analyses were executed, such as inverse variance weighting (IVW), weighted median (WM 1), weighted mode (WM 2), and MR-Egger regression techniques. Furthermore, we carried out co-localization analyses utilizing the GWAS summary statistics for both MTX and PD in order to comprehensively evaluate the causal relationship between MTX and the risk of developing PD.</div></div><div><h3>Results</h3><div>The MR analysis revealed a positive causal connection between methotrexate (MTX) and a decreased likelihood of developing Parkinson's disease (PD). In particular, the IVW method showed a negative association between MTX use and PD incidence, indicating that MTX is linked to a lower risk of PD (OR = 4.78E−11, 95 % CI = 1.06E−19 to 2.16E−02, <em>p</em> = 1.94E−08). Similar findings were acquired through the WM 1, WM 2, and MR-Egger methodologies. Additionally, COLOC analysis indicated a shared genetic variant between MTX and PD at a specific locus.</div></div><div><h3>Conclusion</h3><div>The results from this joint MR and COLOC research indicate a possible causal link between the use of methotrexate and the likelihood of developing Parkinson's disease. Nonetheless, further research and confirmation of these results, as well as an examination of potential mechanisms, are necessary.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114386"},"PeriodicalIF":4.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Levomilnacipran alleviates cyclophosphamide-induced hepatic dysfunction in male Wistar albino rats; emerging role of α-Klotho/TLR4/p38-MAPK/NF-κB p65 and caspase-3-driven apoptosis trajectories
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-08 DOI: 10.1016/j.intimp.2025.114384
Ehab E. Sharata , Mina Ezzat Attya , Marwa M. Khalaf , Remon Roshdy Rofaeil , Amira M. Abo-Youssef , Ramadan A.M. Hemeida
{"title":"Levomilnacipran alleviates cyclophosphamide-induced hepatic dysfunction in male Wistar albino rats; emerging role of α-Klotho/TLR4/p38-MAPK/NF-κB p65 and caspase-3-driven apoptosis trajectories","authors":"Ehab E. Sharata ,&nbsp;Mina Ezzat Attya ,&nbsp;Marwa M. Khalaf ,&nbsp;Remon Roshdy Rofaeil ,&nbsp;Amira M. Abo-Youssef ,&nbsp;Ramadan A.M. Hemeida","doi":"10.1016/j.intimp.2025.114384","DOIUrl":"10.1016/j.intimp.2025.114384","url":null,"abstract":"<div><h3>Aim</h3><div>This study aims to investigate the potential protective effect of levomilnacipran (LVM) against cyclophosphamide (CPA)-induced hepatotoxicity by targeting α-Klotho/TLR4/p38-MAPK/NF-κB p65 and Caspase-3-dependent apoptosis signaling pathways.</div></div><div><h3>Main methods</h3><div>The toxicity of CPA was assessed using biochemical analysis of the serum hepatotoxicity parameters (AST, ALT, and direct bilirubin) and histopathological examination. Hepatic MDA and SOD were evaluated. The ELISA procedure was employed to evaluate the levels of hepatic TNF-α, IL-1β, and IL-18, hepatic caspase-3, and serum α-Klotho. The expression of hepatic TLR4 and NF-κB p65 was examined using an immunohistochemical technique. A western blot assay was used to determine the expression of MYD88, and p38-MAPK.</div></div><div><h3>Key findings</h3><div>LVM abrogated CPA-induced hepatotoxicity by reducing the elevated hepatoxicity markers and mitigating the histopathological aberrations. It also lowered MDA content and increased SOD activity. Furthermore, it reduced TNF-α, IL-1β, and IL-18 contents, as well as caspase-3 activity. Additionally, LVM diminished TLR4, MYD88, NF-κB p65, and p38 MAPK expression and boosted the levels of α-Klotho.</div></div><div><h3>Significance</h3><div>LVM alleviated hepatic injury generated by CPA via downregulating TLR4/p38 MAPK/NF-κB p65 signaling cascade through the participation of α-Klotho, as well as inhibiting caspase-3-driven apoptosis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114384"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lysozyme modulates inflammatory responses to exacerbate the severity of rheumatoid arthritis
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-08 DOI: 10.1016/j.intimp.2025.114427
Hao Xu , Luxu Yin , Liang Zou , Enshui Zhang , Yang Cheng , Wenyue Zhang , Yihong Liu , Jinxiang Han , Yan Zhao
{"title":"Lysozyme modulates inflammatory responses to exacerbate the severity of rheumatoid arthritis","authors":"Hao Xu ,&nbsp;Luxu Yin ,&nbsp;Liang Zou ,&nbsp;Enshui Zhang ,&nbsp;Yang Cheng ,&nbsp;Wenyue Zhang ,&nbsp;Yihong Liu ,&nbsp;Jinxiang Han ,&nbsp;Yan Zhao","doi":"10.1016/j.intimp.2025.114427","DOIUrl":"10.1016/j.intimp.2025.114427","url":null,"abstract":"<div><h3>Background</h3><div>The mechanisms underlying Rheumatoid Arthritis (RA) remain unclear. Despite having relatively well-defined treatment strategies, current therapeutic approaches only achieve a remission rate of 70 %–80 %, with poor prognosis and no clear diagnostic criteria for early RA. Therefore, there is a need for new therapeutic targets or biomarkers to improve the treatment of RA.</div></div><div><h3>Methods</h3><div>Firstly, we identified the expression characteristics of lysozyme (LYZ) in early RA patients through plasma proteomics and synovial fluid single-cell sequencing analysis. Secondly, we constructed Lyz1 cKO mice to investigate the role of Lyz1 in RA pathogenesis using the Collagen Antibody-Induced Arthritis (CAIA) mouse model. Thirdly, we silenced LYZ to clarify its impact on TNF-α-induced inflammatory cytokine release and other inflammatory phenotypes in MH7A cells. Finally, we explored the cellular pathways involving LYZ in fibroblast-like synoviocytes (FLSs) and changes in RA-related genes through RNA sequencing (RNA-Seq).</div></div><div><h3>Results</h3><div>LYZ was highly expressed in the plasma and synovial macrophages of early RA patients. The absence of Lyz1 reduced the arthritis course and joint damage in CAIA mice. Silencing LYZ promoted the proliferation and apoptosis of MH7A cells and improved their inflammatory phenotypes, possibly through the regulation of the TNF signaling pathway.</div></div><div><h3>Conclusion</h3><div>LYZ is highly expressed in the plasma and synovial fluid macrophages of early RA patients and exacerbates RA progression by modulating inflammation-related pathways, demonstrating potential as a biomarker for early RA diagnosis or a therapeutic target.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114427"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive pan-cancer single-cell analysis reveals glycolysis-related signatures as predictive biomarkers for immunotherapy response and their role in bladder Cancer
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-08 DOI: 10.1016/j.intimp.2025.114381
Yingjie Li, Wenjie Yang, Hualin Chen, Zhaoheng Jin, Jie Dong, Lin Ma, Zhigang Ji
{"title":"Comprehensive pan-cancer single-cell analysis reveals glycolysis-related signatures as predictive biomarkers for immunotherapy response and their role in bladder Cancer","authors":"Yingjie Li,&nbsp;Wenjie Yang,&nbsp;Hualin Chen,&nbsp;Zhaoheng Jin,&nbsp;Jie Dong,&nbsp;Lin Ma,&nbsp;Zhigang Ji","doi":"10.1016/j.intimp.2025.114381","DOIUrl":"10.1016/j.intimp.2025.114381","url":null,"abstract":"<div><div>Glycolysis is a vital metabolic biological process in tumor progression and immune modulation. This study comprehensively investigated the roles of glycolysis in pan-cancer, especially in bladder cancer. Exploration of 34 single-cell RNA sequencing (scRNA-seq) cohorts, eight ICI-treated bulk RNA-seq cohorts, and TCGA bulk pan-cancer RNA-seq cohorts uncovered a Glycolysis.Sig which strongly correlated with immunotherapy response and demonstrated excellent predictive performance in prognosis and immune response. Hub-Glycolysis.Sig exhibited varying interactions with the immune microenvironment based on cancer type. In bladder cancer, higher glycolysis risk scores correlated with poorer prognosis, with distinct immune infiltration characteristics between subtypes. scRNA-seq revealed high glycolysis levels in bladder epithelial cells. <em>COPB2</em> was highly expressed in bladder cancer, promoting cell proliferation, migration, and glycolytic activity in vitro and in vivo. Our large-scale data analysis confirmed the negative correlation between glycolysis and immunotherapy outcomes, identifying Glycolysis.Sig as a novel predictive biomarker. Hub-Glycolysis.Sig provides clinical insights for bladder cancer therapy strategies, while <em>COPB2</em> and other potential therapeutic targets facilitate personalized cancer treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114381"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineering CD3 subunits with endoplasmic reticulum retention signal facilitates allogeneic CAR T cell production
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-07 DOI: 10.1016/j.intimp.2025.114412
Hamidreza Ebrahimiyan , Ali Sayadmanesh , Mahdi Hesaraki , Marzieh Ebrahimi , Hossein Baharand , Mohsen Basiri
{"title":"Engineering CD3 subunits with endoplasmic reticulum retention signal facilitates allogeneic CAR T cell production","authors":"Hamidreza Ebrahimiyan ,&nbsp;Ali Sayadmanesh ,&nbsp;Mahdi Hesaraki ,&nbsp;Marzieh Ebrahimi ,&nbsp;Hossein Baharand ,&nbsp;Mohsen Basiri","doi":"10.1016/j.intimp.2025.114412","DOIUrl":"10.1016/j.intimp.2025.114412","url":null,"abstract":"<div><div>The success of autologous CAR T cell therapies has driven interest in developing off-the-shelf allogeneic CAR T cells as a scalable and readily available option for broader patient access. Most of the current approaches involve the knockout of T cell receptor (TCR) subunits via genome editing for preventing graft-versus-host disease (GvHD). However, clinical translation of these methods faces challenges due to manufacturing complexities and emerging safety concerns like unintended long deletions and chromosomal loss. In this study, we explored an alternative approach by engineering synthetic CD3 subunits containing an endoplasmic reticulum retention (ERR) signal to suppress TCR surface expression by disrupting its trafficking to the plasma membrane. We screened multiple CD3-ERR candidate designs to identify the construct with the highest efficacy in TCR downregulation. The selected candidate, CD3ζ-ERR, was further characterized, demonstrating its ability to minimize TCR-mediated activation and alloreactivity without affecting T cell phenotype, cell cycle and cytokine-induced expansion. Subsequent assays revealed that CD3ζ-ERR CD19 CAR T cells retained their CAR-mediated cytotoxic function against CD19<sup>+</sup> malignant cells. This study presents an alternative approach for TCR downregulation that circumvents genome editing. By using a transgene compatible with conventional viral vector delivery, this approach holds promise for scalable clinical-grade manufacturing of allogeneic CAR T cell therapies.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114412"},"PeriodicalIF":4.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Akkermansia muciniphila protects against dopamine neurotoxicity by modulating butyrate to inhibit microglia-mediated neuroinflammation
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-07 DOI: 10.1016/j.intimp.2025.114374
Kaifei Xu , Guoqing Wang , Jiantao Gong, Xinxing Yang, Yufeng Cheng, Daidi Li, Shuo Sheng, Feng Zhang
{"title":"Akkermansia muciniphila protects against dopamine neurotoxicity by modulating butyrate to inhibit microglia-mediated neuroinflammation","authors":"Kaifei Xu ,&nbsp;Guoqing Wang ,&nbsp;Jiantao Gong,&nbsp;Xinxing Yang,&nbsp;Yufeng Cheng,&nbsp;Daidi Li,&nbsp;Shuo Sheng,&nbsp;Feng Zhang","doi":"10.1016/j.intimp.2025.114374","DOIUrl":"10.1016/j.intimp.2025.114374","url":null,"abstract":"<div><div>Parkinson's disease (PD) is an age-related and second most common neurodegenerative disease. To date, safe and efficient therapeutic drugs are deficient. In recent years, the relationship between gut microbiota and CNS have received more attention. Homeostatic imbalance of gut microbiota was revealed to participate in the progression of PD. This study detected that <em>Akkermansia muciniphila</em> (<em>A. muciniphila</em>) was apparently decreased in the feces of PD rats via 16S rRNA amplicon sequencing. Furtherly, we found that exogenous supplementation of <em>A. muciniphila</em> could improve 6-OHDA-induced motor dysfunction and dopamine (DA) neuronal damage and neuroinflammatory factors release in PD rats. Moreover, the short-chain fatty acids (SCFAs) sequencing demonstrated that <em>A. muciniphila</em> addition increased butyrate content both in gut and brain. The subsequent functional experiments confirmed that the exogenous supplementation of butyrate conferred neuroprotection against DA neurotoxicity. Mechanically, butyrate targeted microglia to attenuate DA neuronal injury via inhibiting microglia activation and neuroinflammatory factors production. In conclusion, <em>A. muciniphila</em> protected DA neuronal damage by modulating butyrate to inhibit microglia-elicited neuroinflammation. These findings provided a potential application of <em>A. muciniphila</em> on PD treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114374"},"PeriodicalIF":4.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Artemisinin regulates cell proliferation, apoptosis, and the inflammatory response of human dental pulp stem cells through the p53 signaling pathway under LPS-induced inflammation
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-07 DOI: 10.1016/j.intimp.2025.114396
Yuan Sui , Xiaofei Dong , Enkang Tong , Cuicui Zhao , Rongrong Nie , Xiangfeng Meng
{"title":"Artemisinin regulates cell proliferation, apoptosis, and the inflammatory response of human dental pulp stem cells through the p53 signaling pathway under LPS-induced inflammation","authors":"Yuan Sui ,&nbsp;Xiaofei Dong ,&nbsp;Enkang Tong ,&nbsp;Cuicui Zhao ,&nbsp;Rongrong Nie ,&nbsp;Xiangfeng Meng","doi":"10.1016/j.intimp.2025.114396","DOIUrl":"10.1016/j.intimp.2025.114396","url":null,"abstract":"<div><h3>Objective</h3><div>The purpose of this study was to investigate the effects and mechanism of artemisinin (ART) on the proliferation, apoptosis, and inflammatory response of human dental pulp stem cells (HDPSCs) under lipopolysaccharide (LPS)-induced inflammation.</div></div><div><h3>Methods</h3><div>HDPSCs were isolated, cultured, and identified by flow cytometry and three-directional differentiation induction. A suitable concentration of LPS was selected to mimic the inflammatory condition in vitro. After culturing with ART and LPS for 48 h, cell proliferation was observed by CCK-8 assay; cell apoptosis was observed by flow cytometry, western blot, and Caspase-3 activity; and the inflammatory response was observed by qRT-PCR and ELISA. Transcriptome sequencing, immunofluorescence staining, qRT-PCR, western blot, and RITA were used to explore the underlying mechanism.</div></div><div><h3>Results</h3><div>HDPSCs were successfully isolated and exhibited the potential for multilineage differentiation. 0.1 μg/mL of LPS was utilized to mimic the inflammatory condition. ART promoted HDPSCs proliferation but repressed apoptosis and the inflammatory response under LPS-induced inflammation. Further, ART exerted its effect through the p53 signaling pathway.</div></div><div><h3>Conclusion</h3><div>ART inhibited the p53 signaling pathway to promote HDPSCs proliferation, but hinder apoptosis and the inflammatory response under LPS-induced inflammation.</div></div><div><h3>Clinical significance</h3><div>This study demonstrates that ART facilitates the alleviation of inflammation and preserves the viability of HDPSCs. Therefore, ART may serve as a promising therapeutic drug for the repair and regeneration of dental pulp in the treatment of deep caries and reversible pulpitis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114396"},"PeriodicalIF":4.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SLAMF7-expressing B cells as crucial mediators in the pathogenesis of rheumatoid arthritis-interstitial lung disease
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-07 DOI: 10.1016/j.intimp.2025.114392
Keke Xie , Qincheng Che , Jie Chen , Hongxing Wang , Bingbing Ren , Xiaorong Chen , Fang Wang , Xiao Wang , Jianing Wang , Qiang Shu
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