Immunopharmacology and Immunotoxicology最新文献

{"title":"Losartan inhibits methotrexate-induced testicular damage <i>via</i> anti-inflammatory and anti-apoptotic effects.","authors":"Somayeh Mohammadi Panah, Mohammad Rafi Khezri, Hojat Ghasemnejad-Berenji, Hemin Ashayeri Ahmadabad, Nafiseh Andishfar, Morteza Ghasemnejad-Berenji","doi":"10.1080/08923973.2026.2625037","DOIUrl":"https://doi.org/10.1080/08923973.2026.2625037","url":null,"abstract":"<p><strong>Background: </strong>Methotrexate (MTX), a potent chemotherapy drug, has restricted clinical utility owing to its capacity to cause significant gonadal damage.</p><p><strong>Objective: </strong>This study investigated the preventive effect of the angiotensin II type 1 receptor (AT1R) antagonist, losartan, against methotrexate-induced testicular damage in rats.</p><p><strong>Methods: </strong>Twenty-four adult male Wistar rats were randomly allocated into four groups (<i>n</i> = 6). The animals were administered MTX (20 mg/kg) with or without losartan treatment (10 mg/kg/day) via intraperitoneal injection. Histopathological examination and ELISA-based assessment of Ang II, AKT, p-AKT, NF-κB, IL-1, TNF-α, and caspase-3 were performed.</p><p><strong>Results: </strong>MTX administration resulted in considerable testicular impairment, characterized by severe degeneration of seminiferous tubules and a 75% elevation in Angiotensin II (Ang II) concentrations inside the testes. Mechanistically, MTX stimulated inflammatory and apoptotic pathways, increasing IL-1 by 255.6%, TNF-α by 200% (<i>p</i> < 0.001), and NF-κB by 214.3%. Furthermore, MTX suppressed the pAKT/AKT survival pathway by 37.6%, decreasing the ratio from 1.25 to 0.78, hence facilitating apoptosis. The co-administration of Losartan (10 mg/kg/day for seven days) markedly mitigated these effects. Losartan brought Ang II levels back to normal, reduced the inflammatory response (IL-1 went up by only 83.3% and TNF-α by 44.4% compared to the control), lowered NF-κB activity, and raised the pAKT/AKT ratio by 62.8% (to 1.27, which is similar to control levels).</p><p><strong>Conclusion: </strong>The findings indicate that the Ang II/AT1R axis is a significant upstream mediator of MTX-induced gonadotoxicity. It connects inflammatory and pro-apoptotic signaling with structural damage to the testes. Our data collectively demonstrate that AT1R inhibition using Losartan successfully mitigates MTX-induced testicular damage by addressing this upstream mechanistic pathway. Losartan has been identified as a viable treatment strategy for preserving male reproductive function following cytotoxic therapy.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-9"},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FKBP5 promotes pro-inflammatory microglial activation and neuronal injury through NF-κB/NLRP3 signaling in convulsive status epilepticus.","authors":"Haiping Zhang, Lin Wu, Ting Su, Mei Yuan","doi":"10.1080/08923973.2026.2725839","DOIUrl":"https://doi.org/10.1080/08923973.2026.2725839","url":null,"abstract":"<p><strong>Background: </strong>Convulsive status epilepticus (CSE) triggers profound neuroinflammatory responses that exacerbate neuronal injury and impair long-term neurological recovery. FKBP5, a co-chaperone protein implicated in immune regulation, has been increasingly recognized as a modulator of inflammatory signaling. However, its role in microglial activation and neuroinflammation during CSE remains elusive.</p><p><strong>Methods: </strong>A pilocarpine-induced mouse model of CSE was established to investigate FKBP5 expression dynamics in microglia. FKBP5 was silenced <i>in vitro</i> by siRNA transfection in primary microglia isolated from CSE model mice. Subsequently, microglia were co-cultured with primary cortical neurons to evaluate the impact of FKBP5-regulated microglial activation on neuronal survival and inflammatory response. Western blotting, immunofluorescence, and quantitative PCR were used to assess microglial activation phenotype markers, NF-κB activation, and NLRP3 inflammasome-related priming.</p><p><strong>Results: </strong>FKBP5 expression was markedly upregulated in microglia following CSE, correlating with an enhanced pro-inflammatory phenotype and increased pro-inflammatory cytokine production. FKBP5 knockdown suppressed NF-κB activation, reduced NF-κB p65 nuclear translocation, and decreased NLRP3 inflammasome-related protein expression. In primary microglia, FKBP5 knockdown attenuated CSE-associated pro-inflammatory activation and decreased secretion of IL-1β and TNF-α. In microglia-neuron co-culture, FKBP5 knockdown reduced neuronal apoptosis and inflammatory injury, suggesting an indirect role of FKBP5 in modulating neuroinflammation and neuronal damage in the CSE context.</p><p><strong>Conclusion: </strong>Our study identifies FKBP5 as an upstream modulator of NF-κB/NLRP3 signaling in microglia during convulsive status epilepticus. Targeting FKBP5 may represent a promising strategy to ameliorate neuroinflammation and neuronal injury in epilepsy.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-15"},"PeriodicalIF":3.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N6-methyladenosine-modified circ_0081069: an effective approach to modulate breast cancer's tumor immune microenvironment.","authors":"Jinghui Peng, Yue Huang, Wentong Fang, Mingjie Zheng","doi":"10.1080/08923973.2026.2725841","DOIUrl":"https://doi.org/10.1080/08923973.2026.2725841","url":null,"abstract":"<p><strong>Background: </strong>Circular RNA (circRNA) has been recognized as critical regulator in cancer progression. However, the mechanisms of circ_0081069 in breast cancer (BC) remain understood. The study was designed to elucidate the pathological significance and mechanism of circ_0081069 in BC.</p><p><strong>Material and methods: </strong>The expression of circ_0081069 was investigated in BC tissues and cell <i>via</i> qRT-PCR. CCK-8 and Transwell were carried out for assessing cell viability and invasion. After transfection, the expression of circ_0081069, microRNA (miR)-1286 and E2F4 were manipulated, and the mechanism in BC were explored by bioinformatic predication, luciferase reporter assay and RIP assay. The m⁶A modification was confirmed <i>via</i> MeRIP assay. Granzyme, IFN-γ, TNF-α and PD-L1 levels were determined using ELISA and western blot. Xenograft tumor model was established to detect circ_0081069 functions <i>in vivo</i>.</p><p><strong>Results: </strong>Circ_0081069 was markedly upregulated in BC tissues (<i>n</i> = 60) and cells, which was correlated with poor patient prognosis. Knockdown of circ_0081069 restrained MDA-MB-231 and BT549 cells viability and invasion. Moreover, Granzyme, TNF-α, IFN-γ and PD-L1 levels were elevated in the co-cultured BC and CD8⁺ T cells. Mechanistically, circ_0081069 was a sponge for miR-1286, leading to up-regulation of E2F4. The inhibitory functions of circ_0081069 knockdown in BC pathological behaviors and tumor microenvironment were reversed by miR-1286 inhibition. METTL3 silence inhibited cell viability, invasion and tumor microenvironment by stabilizing circ_0081069. Furthermore, circ_0081069 knockdown suppressed BC cell proliferation and regulated immune microenvironment <i>in vivo.</i></p><p><strong>Conclusions: </strong>m⁶A-modified circ_0081069 facilitated BC progression and tumor microenvironment <i>via</i> the miR-1286/E2F4 regulatory axis.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-16"},"PeriodicalIF":3.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nephroprotective effect of vitamin and sodium selenite against azithromycin-induced renal toxicity in a rat model: attenuation of oxidative stress, inflammation, and apoptosis.","authors":"Marwan A Ibrahim, Ibrahim M Ibrahim Laila, Ayman M Algohary, Mai M Anwar","doi":"10.1080/08923973.2026.2725032","DOIUrl":"10.1080/08923973.2026.2725032","url":null,"abstract":"<p><strong>Background: </strong>Azithromycin (AZM), a widely prescribed macrolide antibiotic, has been increasingly associated with nephrotoxicity mediated by oxidative stress, inflammation, and apoptosis. Antioxidants such as Vitamin E and Sodium Selenite may exert protective effects against drug-induced nephrotoxicity.</p><p><strong>Objectives: </strong>This study aimed to investigate the nephrotoxic effects of AZM and the possible ameliorative effects of Vitamin E and Sodium Selenite in a rat model.</p><p><strong>Methods: </strong>Thirty adult male Wistar rats (180-200 g) were randomly allocated into five groups (<i>n</i> = 6): control, Vitamin E (100 mg/kg/day), Sodium Selenite (0.25 mg/kg/day), AZM (30 mg/kg/day), and AZM+ Vitamin E + Sodium Selenite. All treatments were administered orally once daily for 14 days. Renal function biomarkers (serum urea and creatinine) and hemoglobin levels were assessed. Kidney tissues were analyzed for oxidative stress markers (MDA, ROS, protein carbonyl, 8-OHdG), inflammatory mediators (MPO, NO, TNF-α), and apoptotic markers (caspase-3, cytochrome-c, p53), together with histopathological examination and apoptotic staining. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test <b>(</b><i>p</i> < 0.05<b>)</b>.</p><p><strong>Results: </strong>AZM administration significantly elevated renal function markers, oxidative stress indices, inflammatory cytokines, and apoptotic signaling, accompanied by marked histopathological injury and increased caspase-3 expression. Conversely, co-administration of Vitamin E and Sodium Selenite markedly attenuated detected biochemical alterations, improved renal functions, and restored renal architecture.</p><p><strong>Conclusion: </strong>Subacute AZM exposure induces significant functional and histopathological renal alterations. Co-administration of Vitamin E and Sodium Selenite confers marked nephroprotection mediated through antioxidant and anti-apoptotic actions. These findings suggest combined therapeutic potential in attenuating AZM-induced renal toxicity.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-16"},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained clinical quiescence in anti-Scl-70 positive systemic sclerosis during long-term entecavir therapy: a potential role for NLRP3 inflammasome inhibition?","authors":"Angelo Nigro","doi":"10.1080/08923973.2026.2725840","DOIUrl":"10.1080/08923973.2026.2725840","url":null,"abstract":"","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-3"},"PeriodicalIF":3.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of histamine H4 receptor antagonist on the inflammatory responses in B cells in a mouse model of multiple sclerosis.","authors":"Haneen A Al-Mazroua, Hussain N Alhamami, Ahmed Nadeem, Mushtaq A Ansari, Saleh A Bakheet, Sabry M Attia, Wedad S Sarawi, Hatun A Alomar, Abdulaziz M S Alsaad, Ali A Alshamrani, Sheikh F Ahmad","doi":"10.1080/08923973.2026.2723386","DOIUrl":"10.1080/08923973.2026.2723386","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) driven by autoimmune mechanisms. However, growing evidence indicates that B lymphocytes may contribute to the disease through antigen presentation and the production of proinflammatory mediators. This study aimed to examine the effect of JNJ 10191584 (JNJ), a potent and selective H4R antagonist, on EAE progression and to uncover the underlying mechanisms.</p><p><strong>Methods: </strong>The research explored the potential impact of H4R antagonists on inflammatory responses in B cells within an EAE mouse model of MS. EAE mice received an oral dose of JNJ at 6 mg/kg daily, starting on day 10 and continuing until day 42. Flow cytometry assessed JNJ's effect on the expression of NF-κB p65, IκBα, Notch1, Notch3, IL-2, IL-6, GM-CSF, iNOS, TNF-α, and MCP-1 in CD19⁺ B cells. We used RT-PCR to assess the impact of JNJ on mRNA levels of these inflammatory markers in brain tissue.</p><p><strong>Results: </strong>In EAE mice, JNJ treatment reduced the number of CD19⁺ cells expressing NF-κB p65, IκBα, Notch1, Notch3, IL-2, IL-6, GM-CSF, iNOS, and MCP-1. Additionally, JNJ decreased mRNA expression of inflammatory markers in brain tissue compared with vehicle-treated mice.</p><p><strong>Conclusions: </strong>These results suggest that targeting H4R with antagonists could offer a new therapeutic approach for MS by specifically modulating B-cell-mediated inflammation.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-10"},"PeriodicalIF":3.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosuvastatin and engeletin ameliorate acetic acid-induced ulcerative colitis through modulation of TXNIP/NLRP3-related inflammatory signaling pathway.","authors":"Thanaa A El-Masry, Sally E Abu-Risha, Walaa A Negm, Eman Aly Kamal","doi":"10.1080/08923973.2026.2716666","DOIUrl":"10.1080/08923973.2026.2716666","url":null,"abstract":"<p><strong>Introduction: </strong>Mucosal inflammation is the defining feature of ulcerative colitis (UC), which is a chronic inflammatory bowel disease. The goal of this study was to determine the involvement of the TXNIP/NLRP3 inflammatory pathway in UC development and to assess the therapeutic potential of engeletin and rosuvastatin.</p><p><strong>Material and methods: </strong>Acetic acid (AA) was used to initiate UC. The animals were divided into seven groups: normal control, UC control, UC treated with mesalazine (100 mg/kg/day), UC treated with rosuvastatin (20 mg/kg/day), UC treated with engeletin (25 mg/kg/day), UC treated with engeletin (50 mg/kg/day), and UC treated with a combination of rosuvastatin and engeletin (20 mg and 25 mg/kg/day). All treatments lasted 21 days. Body weight, colon weight, colon length, and weight-to-length ratio were all assessed. ELISA was used to detect IL-1β, MPO, gasdermin-D, NF-κB p65, and TXNIP contents. TXNIP expression was quantified by quantitative real-time PCR, and colon samples were examined histopathologically and immunohistochemically.</p><p><strong>Results: </strong>UC caused significant weight loss, increased colon weight, and a shift in the colon weight-to-length ratio. These changes were associated with elevated inflammatory markers and upregulation of the TXNIP/NLRP3 pathway markers. All measured parameters were significantly improved after treatment with engeletin, rosuvastatin, and their combination, with the combination having the most pronounced therapeutic benefits.</p><p><strong>Conclusion: </strong>In conclusion, this study demonstrated that AA-induced UC was associated with increased expression of TXNIP/NLRP3-related inflammatory markers, which may contribute to the disease pathophysiology. The combination of engeletin and rosuvastatin was associated with downregulation of TXNIP/NLRP3-related inflammatory signaling and amelioration of biochemical and histopathological changes associated with UC.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-14"},"PeriodicalIF":3.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin and phenformin attenuate SARS-CoV-2 spike protein S1-induced endothelial inflammation involving AMPK/NF-κB signaling in HUVECs.","authors":"Gurkan Yigitturk, Dilan Cetinavci, Melike Ozgul Onal, Hulya Elbe, Feral Ozturk","doi":"10.1080/08923973.2026.2671721","DOIUrl":"10.1080/08923973.2026.2671721","url":null,"abstract":"<p><strong>Objective: </strong>COVID-19, caused by SARS-CoV-2, is a systemic disease with vascular involvement. The spike protein subunit 1 (S1) has been suggested to contribute to endothelial dysfunction by modulating AMP-activated protein kinase (AMPK) signaling and nuclear factor kappa B (NF-κB) activation, potentially promoting inflammation, thrombosis, and vascular injury. This study aimed to investigate the effects of metformin and phenformin, biguanide drugs with known AMPK-activating properties, on S1-induced inflammatory responses and AMPK/NF-κB pathway modulation in human umbilical vein endothelial cells (HUVECs).</p><p><strong>Materials and methods: </strong>HUVECs were used as a model of the macrovascular endothelium, which is known to exhibit endothelial dysfunction and inflammation associated with vascular complications in COVID-19. Cells were exposed to the S1 protein for 1 and 24 h, followed by treatment with phenformin (10 µM and 100 µM) or metformin (100 µM and 1000 µM). Cell viability, AMPK activation, NF-κB phosphorylation, and monocyte adhesion were evaluated.</p><p><strong>Results: </strong>S1 exposure was associated with increased endothelial cell viability and NF-κB activity, along with decreased AMPK phosphorylation. Metformin, particularly at 1000 µM, was associated with increased AMPK activity and reduced NF-κB signaling and monocyte adhesion. Phenformin (10 µM and 100 µM) showed similar but less pronounced effects. These findings suggest that the S1 protein may contribute to endothelial dysfunction in HUVECs. Metformin, at higher concentrations, may mitigate these effects through modulation of the AMPK/NF-κB signaling pathway.</p><p><strong>Conclusion: </strong>Metformin may exert protective effects against S1 protein-induced endothelial inflammation and dysfunction <i>via</i> modulation of AMPK/NF-κB signaling. Further studies are needed to confirm these findings.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"552-558"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of oncostatin M and its receptor in the inflammatory pathogenesis of graves' orbitopathy.","authors":"Jeong Woo Park, Soo Hyun Choi, Dongheon Surl, Jaesang Ko, Jin Sook Yoon","doi":"10.1080/08923973.2026.2654604","DOIUrl":"10.1080/08923973.2026.2654604","url":null,"abstract":"<p><strong>Purpose: </strong>Oncostatin M (OSM) and its receptor (OSMR) are implicated in chronic inflammatory diseases. The role of OSM in Graves' orbitopathy (GO) pathogenesis remains unclear. Here, we investigated the role of OSM-OSMR signaling in GO pathogenesis and assessed its potential as a therapeutic target.</p><p><strong>Methods: </strong>Orbital tissues from GO patients and healthy controls were analyzed for OSM, OSMR, and leukemia inhibitory factor receptor (LIFR) expression levels using quantitative real-time PCR. Cultured orbital fibroblasts were treated with recombinant human OSM (rhOSM) and interleukin (IL)-1β to evaluate changes in inflammatory mediator levels and intracellular signaling pathways. OSMR expression was silenced using small interfering RNA. Western blotting was used to assess cytokine and adipogenic marker levels and pathway activation. Adipogenic differentiation was quantified using Oil Red O staining and spectrophotometry.</p><p><strong>Results: </strong>GO orbital tissues showed significantly increased OSM, OSMR, and LIFR expression. IL-1β stimulation induced time-dependent upregulation of OSM and OSMR expression in orbital fibroblasts. rhOSM pretreatment enhanced IL-1β-induced IL-6, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and cyclooxygenase-2 expression while selectively suppressing IL-8 expression. OSMR silencing reduced inflammatory mediator expression and decreased phosphorylation of Janus kinase 2 and mitogen-activated protein kinase components (JNK, ERK, and p38). OSMR knockdown impaired adipogenic differentiation and downregulated terminal adipocyte marker levels, including adipocyte protein 2 and adiponectin.</p><p><strong>Conclusion: </strong>OSM-OSMR signaling amplifies IL-1β-induced inflammatory responses and promotes terminal adipogenic differentiation in GO orbital fibroblasts. This dual regulatory function suggests OSMR as a novel therapeutic target for modulating inflammation and tissue remodeling in GO.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"528-538"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylation-modified genes regulating macrophage polarization through signaling pathways to mediate sepsis-induced myocardial cell injury.","authors":"Yueming Wu, Liuhua Pan, Jing Zhao, Shunnan Sun, Xuntao Deng, Hua Chen, Junlong Xu","doi":"10.1080/08923973.2026.2673959","DOIUrl":"10.1080/08923973.2026.2673959","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a systemic inflammatory response caused by infection, often accompanied by myocardial injury. Studies have shown that methylation modifications are associated with immune cell polarization, but their role in sepsis-induced myocardial injury remains unclear. This article aimed to investigate how methylation modifications regulate macrophage polarization through the phosphoinositide 3-kinase/protein kinase B/mammalian target of Rapamycin (PI3K/AKT/mTOR) signaling pathway, thereby influencing sepsis-induced myocardial injury.</p><p><strong>Methods: </strong>Sepsis was induced by lipopolysaccharide (LPS), and interventions included methylation inhibition, PI3K inhibition, and Interleukin-10 (IL-10) overexpression. Myocardial injury and immune responses were assessed by measuring physiological indicators, myocardial injury markers, hematoxylin-eosin (HE) staining, immunohistochemistry, and immunological assays in rats.</p><p><strong>Results: </strong>After sepsis induction, myocardial injury was more pronounced in the methylation inhibition and PI3K inhibition groups, while the IL-10 overexpression group exhibited milder injury. Immunological assays showed that the proportion of M1 macrophages was increased in the methylation and PI3K inhibition groups, while the IL-10 overexpression group maintained a higher proportion of M2 macrophages.</p><p><strong>Conclusion: </strong>Methylation modifications could regulate macrophage polarization through PI3K-related signaling pathways, thereby aggravating sepsis-induced myocardial injury.IL-10, by promoting M2 macrophage function, attenuates myocardial injury and holds potential therapeutic value.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"729-737"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}