International immunopharmacology最新文献

{"title":"Role of sacubitril/valsartan in modulating diabetes mediated cognitive and neuronal impairment","authors":"Mai M. Al-Ashram ,&nbsp;Manar A. Nader ,&nbsp;Ahmed R. El-Sheakh","doi":"10.1016/j.intimp.2025.114431","DOIUrl":"10.1016/j.intimp.2025.114431","url":null,"abstract":"<div><div>Earlier investigations had established that Diabetes mellitus (DM) caused significant damage in the central nervous system, bringing about diabetic encephalopathy and increasing the risk of cognitive-related problems. Nonetheless, the inherent pathophysiology of cognitive dysfunctions in DM is not well understood. The current study aimed to examine the possible influences of sacubitril/valsartan (SAC/VAL), an angiotensin receptor blocker/neprilysin inhibitor (ARNI), on cognitive dysfunction associated with streptozotocin (STZ)-induced diabetic rats. SAC/VAL and VAL treatments were initiated three days after the diabetic condition was established and continued daily for eight weeks. Normal, non-diabetic rats were reserved as a control group. Both SAC/VAL and VAL treatment in diabetic rats ameliorated diabetes induced oxidative stress as indicated by reduced malondialdehyde (MDA), increased total antioxidant capacity (TAO) in hippocampal tissue and decreased serum advanced glycation end products (AGEs), also inflammatory and apoptotic changes were observed and proved by the reduction of tumor necrosis factor alpha (TNF-α) and caspase −3 in rat hippocampus. SAC/VAL administration to diabetic rats also improved neuronal damages as reflected by restored cAMP response element-binding protein (CREB), brain derived neurotrophic factor (BDNF) and pre-synaptic phosphoproteins, synapsin I and growth associated protein-43 (GAP-43) in the hippocampus of diabetic rats. Additionally, SAC/VAL treated diabetic rats markedly reduced signs of cognitive deterioration during the Morris water maze test. Collectively, these findings suggested that SAC/VAL might play a vital role in improvement of the cognitive impairment observed in diabetic rats through antioxidant, anti-inflammatory and anti-apoptotic actions.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114431"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726305","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}

{"title":"Lycium barbarum glycopeptide attenuates intracerebral hemorrhage-induced inflammation and oxidative stress via activation of the Sirt3 signaling pathway","authors":"Chang-Sheng Ma ,&nbsp;Bo Han ,&nbsp;Shu-Chen Meng ,&nbsp;Min Bai ,&nbsp;Wen-Jing Yi ,&nbsp;Li-Ying Zhang ,&nbsp;Meng-Yuan Duan ,&nbsp;Yi-Jun Wang ,&nbsp;Mao-Tao He","doi":"10.1016/j.intimp.2025.114518","DOIUrl":"10.1016/j.intimp.2025.114518","url":null,"abstract":"<div><h3>Background</h3><div>Intracerebral hemorrhage (ICH) is a severe neurological condition characterized by high morbidity and mortality rates, with no effective treatment currently available. <em>Lycium barbarum</em> glycopeptide (LbGP), derived from the further purification of <em>Lycium barbarum</em> polysaccharides (LBP), has demonstrated anti-inflammatory effects, suggesting its potential as a therapeutic agent for ICH. However, the role and mechanisms of LbGP in ICH remain unclear. This study aimed to investigate the effects of LbGP on ICH and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>A collagenase injection-induced mouse model of ICH was used to evaluate the therapeutic effects of LbGP. Mice were treated with varying doses of LbGP, and outcomes were assessed based on hemorrhage volume, neurological function, inflammation, and oxidative stress markers. Apoptosis was analyzed using TUNEL staining. Mechanistic studies focused on mitochondrial acetylation homeostasis and the expression of Sirt3, a mitochondrial deacetylase. Statistical analyses were performed using one-way ANOVA with Tukey's post hoc tests.</div></div><div><h3>Results</h3><div>LbGP administration reduced hemorrhage volume and improved neurological function in a dose-dependent manner. It significantly decreased pro-inflammatory cytokines (IL-18, TNF-α, IL-1β) and oxidative stress markers (malondialdehyde and reactive oxygen species) while increasing superoxide dismutase activity and total antioxidant capacity. LbGP treatment also mitigated apoptosis and promoted mitochondrial acetylation homeostasis. Mechanistically, LbGP upregulated mitochondrial Sirt3 expression, and blocking Sirt3 disrupted mitochondrial acetylation homeostasis, resulting in increased inflammation and oxidative stress.</div></div><div><h3>Conclusions</h3><div>LbGP alleviates inflammation and oxidative stress in hemorrhagic brain injury by activating Sirt3 and maintaining mitochondrial acetylation homeostasis. These findings highlight the therapeutic potential of LbGP in treating ICH, providing a foundation for further clinical applications.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114518"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714866","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}

{"title":"Lonicerin regulates AMPK/SIRT1/autophagy pathway to attenuate heat stress intestinal injury and inhibit inflammation","authors":"Hui Sun ,&nbsp;Long-hui Zhang ,&nbsp;Jin-hao Wang ,&nbsp;Ran Chen ,&nbsp;Ying Liu ,&nbsp;Peng-cheng Zhang ,&nbsp;Chao Niu","doi":"10.1016/j.intimp.2025.114549","DOIUrl":"10.1016/j.intimp.2025.114549","url":null,"abstract":"<div><div>Intestinal injury is one of the most prevalent complications following heat stress (HS) in both humans and animals. Autophagy has been shown to maintain intestinal homeostasis, and modulation of autophagy may help alleviate intestinal injury caused by HS. Lonicerin (LN) are flavonoids known to have enhanced autophagy and anti-inflammatory effects. However, how LN prevent intestinal damage and regulate autophagy after HS remains unknown. The aim of this study was to elucidate the potential regulatory effects of LN on intestinal inflammation and intestinal barrier function in a HS model, and to elucidate the underlying molecular mechanisms. Firstly, we searched for the same inflammatory cytokines in the drug and disease targets through network pharmacology, and <em>in vitro</em> and <em>in vivo</em> experiments showed that LN significantly inhibited the production of pro-inflammatory cytokines. Then it was demonstrated that LN alleviates HS induced intestinal mucosal barrier damage by repairing tight junctions, goblet cells, and mucins in the colon of rats, consistent with the findings of <em>in vitro</em> experiments. In addition, LN reversed HS-induced reduced autophagic flux and maintained autophagic homeostasis <em>via</em> the AMP-activated protein kinase (AMPK)-Silent information regulator 1 (SIRT1) pathway in intestinal epithelial cells and intestinal system. In summary, this study demonstrated that LN exert intestinal protective and immunomodulatory effects by inhibiting the production of pro-inflammatory cytokines, maintaining the integrity of the intestinal mucosal barrier, and the level of AMPK-SIRT1 autophagy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114549"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726307","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}

{"title":"SLC35A2-mediated bisected GlcNAc-modified extracellular vesicles enhance immune regulation in breast cancer lung metastasis","authors":"Yangyang Li ,&nbsp;Tao Guo ,&nbsp;Juntong He ,&nbsp;Defeng Liu ,&nbsp;Shihao Peng ,&nbsp;Aman Xu","doi":"10.1016/j.intimp.2025.114505","DOIUrl":"10.1016/j.intimp.2025.114505","url":null,"abstract":"<div><div>This study investigates the role of SLC35A2-mediated bisected GlcNAc-modified small extracellular vesicles (sEVs) in breast cancer (BC) lung metastasis. By modulating B3GALT1 expression, these sEVs regulate the pre-metastatic immune microenvironment, enhancing CD8+ T cell infiltration and reducing immune evasion. The use of β-peptide-loaded sEVs further amplifies anti-metastatic effects, as demonstrated <em>in vivo</em> mouse models and molecular analyses. These findings underscore the therapeutic potential of glycosylation-modified sEVs in enhancing immune responses and controlling BC metastasis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114505"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726306","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}

{"title":"β-Sitosterol suppresses NLRP3 Inflammasome activation and Pyroptosis in myocardial ischemia/reperfusion injury via inhibition of PPARγ2","authors":"Zheyi Wu ,&nbsp;Niwen Huang ,&nbsp;Chao Li ,&nbsp;Muzhi Lin ,&nbsp;Zhangrong Chen ,&nbsp;Wei Li ,&nbsp;Haiyan Zhou","doi":"10.1016/j.intimp.2025.114543","DOIUrl":"10.1016/j.intimp.2025.114543","url":null,"abstract":"<div><h3>Background</h3><div>β-Sitosterol, a plant-derived sterol, has demonstrated potential therapeutic effects in cardiovascular diseases, particularly myocardial ischemia-reperfusion injury (MIRI). Our study investigates its underlying mechanism through regulation of pyroptosis.</div></div><div><h3>Methods</h3><div>To understand the role of β-sitosterol in protecting cardiomyocytes, MIRI rats were treated with β-sitosterol. Rats' cardiac functions were monitored, and hearts were harvested for histology and Western Blot analysis. Immunofluorescence, immunoblot, enzyme-linked immunosorbent assay, as well as overexpression and knockdown techniques were utilized in this study to investigate the molecular mechanisms underlying the cardioprotective effects of β-sitosterol.</div></div><div><h3>Results</h3><div>Our results showed that β-Sitosterol significantly reduced H/R-induced pyroptosis in cardiomyocytes by decreasing cleaved caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18). Immunofluorescence staining confirmed suppression of NLRP3 inflammasome activation. Notably, β-Sitosterol inhibited pyroptosis induced by ATP and ATP/LPS through the regulation of PPARγ2. Moreover, PPARγ2 upregulation promoted ATP and ATP/LPS-induced pyroptosis through the NLRP3/caspase-1/GSDMD pathway. In vivo, β-sitosterol alleviates myocardial ischemia-reperfusion injury-induced cardiac dysfunction and myocardial fibrosis in rats.</div></div><div><h3>Conclusions</h3><div>These findings provide new evidence supporting β-sitosterol as a potential therapeutic agent for cardiovascular diseases involving ischemic injury. Its protective effects may be mediated through targeting PPARγ2 and modulating NLRP3-dependent pyroptosis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114543"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714659","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}

{"title":"Corrigendum to “Brain-derived extracellular vesicles mediate systemic coagulopathy and inflammation after traumatic brain injury” [International Immunopharmacology 130 (2024) 111674]","authors":"Fanjian Li ,&nbsp;Lei Li ,&nbsp;Ruilong Peng ,&nbsp;Chuan Liu ,&nbsp;Xiao Liu ,&nbsp;Yafan Liu ,&nbsp;Cong Wang ,&nbsp;Jianye Xu ,&nbsp;Qiaoling Zhang ,&nbsp;Guili Yang ,&nbsp;Ying Li ,&nbsp;FangLian Chen ,&nbsp;Shenghui Li ,&nbsp;Weiyun Cui ,&nbsp;Li Liu ,&nbsp;Xin Xu ,&nbsp;Shu Zhang ,&nbsp;Zilong Zhao ,&nbsp;Jianning Zhang","doi":"10.1016/j.intimp.2025.114514","DOIUrl":"10.1016/j.intimp.2025.114514","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114514"},"PeriodicalIF":4.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729981","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}

{"title":"Melatonin alleviates retinal injury induced by vigabatrin and partially enhances its antiepileptic effects","authors":"Mengdie Ma ,&nbsp;Min Fan ,&nbsp;Songlin Xu ,&nbsp;Qiang Zheng ,&nbsp;Chuanyu Wang ,&nbsp;Pengquan Chen ,&nbsp;Yadong Wei ,&nbsp;JinFang Ge","doi":"10.1016/j.intimp.2025.114516","DOIUrl":"10.1016/j.intimp.2025.114516","url":null,"abstract":"<div><div>Structural optimization and combinational use with additive agents might help expand the clinical use of vigabatrin (VGB). Aiming to investigate the combinational effect of melatonin (MLT) on the antiepileptic action and retinal damage of VGB, a rat epilepsy model was induced by intraperitoneal injection of kainic acid (KA) and evaluated via both Racine grading and electroencephalogram (EEG). MLT (5, 10, 20 mg/kg) and VGB (50, 150 mg/kg) were administered intragastrically for 4 weeks, alone or together. The behavioral performance was measured during the remission of seizures via a series of tasks including the open field test (OFT), beam walking test (BW), Y-maze, and novel object recognition test (NOR). The morphological changes of the hippocampus and retina were observed using HE, Nissl, or immunofluorescence staining. Furthermore, the expression of proteins associated with synaptic plasticity and the Wnt/β-catenin/GSK3β signaling pathway were assessed. The results showed that intraperitoneal injection of KA could induce not only seizure, but also long-term behavioral impairments of sense, motion, and learning and memory in rats. Moreover, VGB could alleviate the neuroinflammation and balance the expression of synaptic plasticity and Wnt/β-catenin/GSK3β pathway proteins of epileptic rats. A combination of MLT couldn't enhance the effect of VGB in prolonging the seizure latency but presented an additive effect in alleviating the seizures grading V and improving the behavioral performance in the BW. Crucially, the combination of MLT considerably reduced the retinal cell damage caused by VGB. These results suggested that MLT could be a beneficial combination for VGB in the treatment of epilepsy, which might provide fresh insight into the clinical application of VGB and MLT.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114516"},"PeriodicalIF":4.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715233","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}

{"title":"Identifying cardiovascular toxicity associated with sphingosine 1-phosphate receptor modulators: A case-control study based on the FDA adverse event reporting system","authors":"Ying Li ,&nbsp;Jingmin Zhang ,&nbsp;Guangrui Yang ,&nbsp;Shujie Jiao ,&nbsp;Mingyuan Guan","doi":"10.1016/j.intimp.2025.114520","DOIUrl":"10.1016/j.intimp.2025.114520","url":null,"abstract":"<div><h3>Introduction</h3><div>Cardiovascular events represent a significant safety concern associated with sphingosine 1-phosphate receptor (S1PR) modulators. However, as S1PR modulators are primarily indicated for rare diseases characterized by multiple complex confounding factors, evidence regarding potential or long-term cardiovascular risks related to these drugs remains limited. This study aimed to comprehensively assess cardiovascular safety signals associated with S1PR modulators.</div></div><div><h3>Methods</h3><div>This case-control study was conducted based on the FDA adverse event reporting system (FAERS) database. The dataset included reports from September 10, 2010 to September 30, 2023. Reporting odds ratios (ROR) were calculated by logistic regression in four different models to examine the robustness of the results. Additionally, to assess adverse event profiles based on clinical trial data, a systematic literature review and subsequent data synthesis were conducted.</div></div><div><h3>Results</h3><div>We included 81,077 cases treated with S1PR modulators (median [IQR] age, 45 [36–54]; 60,245 [74.31 %] female), and 12,087,627 cases with no prior use of S1PR modulators as comparators. Besides signals of hypertension and bradyarrhythmias, QT interval prolongation in the fingolimod group (ROR = 1.92 [95 % CI, 1.73–2.12]; <em>P</em> &lt; 0.001), and central nervous system ischemia in the siponimod group (ROR = 1.26 [95 % CI, 1.04–1.52]; <em>P</em> = 0.02) were also detected in all models. Signals of tachyarrhythmias and ischaemic heart disease in the fingolimod group as well as QT interval prolongation in the siponimod group were consistent in all adjusted models.</div></div><div><h3>Conclusion</h3><div>In this study, signals of bradyarrhythmias, hypertension, QT interval prolongation, central nervous system ischemia, tachyarrhythmias, and ischaemic heart disease were significant with one or more S1PR modulators, which warrant clinical attention and ongoing monitoring.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114520"},"PeriodicalIF":4.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706184","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}

{"title":"Structural characterization of raw and wine-steamed Polygonatum cyrtonema Hua oligosaccharides and their bioactivity on immune regulation via modifying the gut microbiota","authors":"Shuanghui Shi ,&nbsp;Jingqiu Zhang ,&nbsp;Junli Zhang,&nbsp;Siyuan Ma,&nbsp;Yufeng Hu,&nbsp;Haiting Zhu,&nbsp;Huinan Wang,&nbsp;Mingrui Jiang,&nbsp;Yingzi Wang","doi":"10.1016/j.intimp.2025.114468","DOIUrl":"10.1016/j.intimp.2025.114468","url":null,"abstract":"<div><div><em>Polygonatum cyrtonema</em> Hua (PC) is a traditional Chinese medicine with a long history of use as pharmaceuticals or functional foods. Wine steaming is the main processing method of PC, which changes the structure of polysaccharides and oligosaccharides in PC and enhances biological activities. This study investigated the structural characterization of raw and wine-steamed PC oligosaccharides and the differences in the immunomodulatory effects using cyclophosphamide (CTX)-induced immunosuppression rat model. The oligosaccharides content and molecular weight of PC after wine steaming decreased, the proportion of oligosaccharides in total sugars and the reducing sugars content increased, and the monosaccharides composition of oligosaccharides changed. The raw <em>Polygonatum cyrtonema</em> Hua oligosaccharides (PCCO) and the wine-steamed <em>Polygonatum cyrtonema</em> Hua oligosaccharides (PCWO) exerted regulatory effects on organ index, immunoglobulin G (IgG), complement 3 (C3) spleen and colon tissue morphology, hematopoietic function of immunosuppressive rats treated by cyclophosphamide (CTX). Both PCCO and PCWO significantly regulated and improved the diversity and abundance of gut microbiota in immunosuppressed rats and increased the content of short-chain fatty acids (SCFAs) in the feces of rats, and the regulating effect of PCWO was better than PCCO. Differential microbiota analysis showed that PCWO could promote the proliferation of <em>Bifidobacterium</em>, <em>Bacteroides</em>, <em>Oscillibacter</em>, <em>Roseburia</em>, and <em>Alistipes</em>. In summary, the difference in the structural characteristics of PC oligosaccharides might be the reason for immune enhancement. This study could provide a theoretical basis for clarifying the scientific connotation of wine steaming to enhance the efficacy of PC, and promote the application of wine-steamed PC as an immunomodulator in pharmaceuticals or functional foods.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114468"},"PeriodicalIF":4.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706186","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}

{"title":"PM2.5 regulates TGF-β1/Smads-mediated pulmonary fibrosis via ROS/SnoN in vitro and in vivo","authors":"Xiaohong Li ,&nbsp;Xuan Ma ,&nbsp;Limin Zhang ,&nbsp;Wenbo Wu ,&nbsp;Ruixi Zhou ,&nbsp;Siqi Li ,&nbsp;Yumei Liu ,&nbsp;Fengjiao Tan ,&nbsp;Xiaolin Han ,&nbsp;Qin Wang ,&nbsp;Jinfeng Tan ,&nbsp;Li Yu ,&nbsp;Wanwei Li","doi":"10.1016/j.intimp.2025.114477","DOIUrl":"10.1016/j.intimp.2025.114477","url":null,"abstract":"<div><div>PM2.5 can result in a chronic lung disease, such as pulmonary fibrosis (PF), but the precise mechanism is unclear. In vivo, 40 male C57BL/6 mice were exposed to three concentrations of PM2.5 (0.5 mg/kg·Wt, 5 mg/kg·Wt and 8 mg/kg·Wt) and PM2.5 was administered by tracheal drip every three days for a total of 15 times. Then all mice were euthanized, blood and lung tissue were collected for testing of various indicators. In vitro, rat alveolar type II epithelial cells (RLE-6TN) were pretreated with different concentrations of PM2.5, ROS inhibitor (Vitamin C) and ubiquitin proteasome inhibitor (MG132) separately. Our results indicated that PM2.5 resulted in inflammation and oxidative stress, which in turn caused pathological damage and collagen deposition of lung tissue. In addition, exposure to PM2.5 increased TGF-β1 protein expression and Smad3 phosphorylation both in cells and in lung tissue, which involved collapse of antioxidant reduction system and degradation of SnoN. Additionally, in order to explored potential mechanisms, we used MG132 and VC pretreated cells and found that MG132 and VC pretreatment both inhibited ROS production, and increased SnoN protein expression levels. Further testing of EMT related indicators revealed that MG132 and VC pretreatment reversed the changes under PM2.5 exposure. Moreover, MG132 pretreatment reversed the increase of TGF-β1 protein expression and the Smad3 phosphorylation induced by PM2.5, but the effects were not as strong as those of VC pretreatment, which was related to the fact that VC inhibited both ROS production and SnoN degradation, which further clarifies the key role of ROS and SnoN in PM2.5-induced EMT. Therefore, this study conjectured that ROS/SnoN functioned as a key regulating factor in PM2.5-induced PF and EMT.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114477"},"PeriodicalIF":4.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706185","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}