International immunopharmacology最新文献

{"title":"Polysaccharide extracted from Polygonatum kingianum Coll. Et Hemsl. Activates macrophages via the TLR4/NF-κB/MAPK pathway and exhibits vaccine adjuvant effect","authors":"Chaoying Jin ,&nbsp;Biying Ma ,&nbsp;Chao Zhong ,&nbsp;Litao Jia ,&nbsp;Jiaqian Yang ,&nbsp;Wenqi Wang ,&nbsp;Jiahao Liu ,&nbsp;Ying Zhou ,&nbsp;Rui Zhu ,&nbsp;Bo Yang ,&nbsp;Yiqi Wang","doi":"10.1016/j.intimp.2025.115585","DOIUrl":"10.1016/j.intimp.2025.115585","url":null,"abstract":"<div><div><em>Polygonatum kingianum</em> Coll. et Hemsl. (Huang Jing), a traditional Chinese medicinal herb, has long been used as a functional food and immune-enhancing remedy. Its polysaccharide component (PKP) is believed to drive immunomodulatory effects, though the molecular mechanisms behind its adjuvant potential remain unclear. PKP was isolated using water extraction, ethanol precipitation, enzymatic digestion, and purification. The immunostimulatory activity was assessed in vitro using RAW264.7 macrophages and primary macrophages from TLR4^+/+ and TLR4^−/− mice. Cytokine secretion (TNF-α, IL-6), nitric oxide production, and gene/protein expression were evaluated through RT-PCR, Western blotting, and immunofluorescence to analyze the activation of the TLR4/NF-κB/MAPK pathway. In vivo, the adjuvant activity of PKP was tested in BALB/c mice immunized with ovalbumin (OVA), measuring antigen-specific immune responses. The results revealed that PKP robustly activated macrophages in a TLR4-dependent manner, significantly enhancing TNF-α (3.8-fold) and IL-6 (2.5-fold) secretion, and upregulating MyD88, TRIF, p65-NF-κB, and MAPK phosphorylation. TLR4^−/− macrophages showed abolished responses, confirming TLR4 as the critical receptor. PKP also enhanced antigen-specific IgG titers and Th1/Th2 cytokine production (IFN-γ, IL-4) in OVA-immunized mice, demonstrating its adjuvant efficacy. Notably, while PKP exhibited activity at higher in-vitro concentrations than LPS, its low toxicity and plant origin constitute key advantages over bacterial endotoxins; accordingly, PKP should be framed not as a more potent LPS alternative, but as a safer adjuvant candidate for vaccine development. In conclusion, PKP activates macrophages through the TLR4/MyD88/TRIF/NF-κB/MAPK axis and functions as a potent vaccine adjuvant, providing mechanistic validation for its traditional use and positioning it as a promising low-toxicity candidate for improving vaccine-mediated immunity.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115585"},"PeriodicalIF":4.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199124","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":"Phytosphingosine alleviates DSS-induced colitis by regulating the gut microbiota and inflammatory responses","authors":"Ruping Shan ,&nbsp;Kexin Wang ,&nbsp;Qiujie Chen ,&nbsp;Lijuan Bao ,&nbsp;Keyi Wu ,&nbsp;Yihong Zhao ,&nbsp;Yu Han ,&nbsp;Yating Gao ,&nbsp;Naisheng Zhang ,&nbsp;Xiaoyu Hu ,&nbsp;Yunhe Fu ,&nbsp;Caijun Zhao ,&nbsp;Wenchao Bian","doi":"10.1016/j.intimp.2025.115610","DOIUrl":"10.1016/j.intimp.2025.115610","url":null,"abstract":"<div><div>Inflammatory bowel disease is becoming increasingly prevalent and represents a major concern in global public health. However, conventional therapies often come with various adverse effects. Phytosphingosine (PS), a key metabolite in sphingolipid metabolism, is widely found in plants and fungi and possesses notable anti-inflammatory properties. In this study, we aimed to evaluate the protective effects of PS against dextran sulfate sodium (DSS)-induced experimental colitis in mice and elucidate its underlying mechanisms. Our results showed that oral administration of PS significantly alleviated DSS-induced colonic injury and reduced levels of proinflammatory cytokines such as TNF-α and IL-1β. Additionally, PS improved intestinal barrier function disrupted by DSS, as indicated by increased expression of mucin-2 and tight junction proteins. Furthermore, PS suppressed the activation of the NF-κB signaling pathway, oxidative stress and enhanced PPARγ expression. We also observed that PS mitigated DSS-induced gut dysbiosis in mice, characterized by an increase in <em>Bacteroidota</em> and a decrease in <em>Proteobacteria</em>. To explore the role of the gut microbiota in PS-mediated protection against colitis, fecal microbiota transplantation (FMT) was conducted in DSS-treated mice. Recipients of FMT from PS-treated donors exhibited reduced inflammatory responses and improved intestinal integrity, accompanied by a higher abundance of <em>Bacteroidota</em> in the gut. Additionally, PS treatment modified the profile of short-chain fatty acids in the mice, with a notable increase in the levels of butyrate and propionate. Overall, our findings demonstrate that PS attenuates DSS-induced colitis in mice through modulation of the gut microbiota, providing a potential strategy for IBD intervention via microbiota regulation.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115610"},"PeriodicalIF":4.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199094","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":"The role of miR-217/SIRT1 Axis in modulating the NLRP3 Inflammasome in the naturally aging thoracic aorta and in endothelial cells undergoing senescence induced by H2O2","authors":"Dake Huang ,&nbsp;Ke Shen ,&nbsp;Li Gui ,&nbsp;Qiongqiong Cao ,&nbsp;Fangmei Yu ,&nbsp;Yunxia Lu","doi":"10.1016/j.intimp.2025.115570","DOIUrl":"10.1016/j.intimp.2025.115570","url":null,"abstract":"<div><div>Given resveratrol's (RES) potential as an anti-aging agent, this study explored its ability to inhibit the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome through the miR-217/SIRT1 axis in senescent endothelial cells. Male C57BL/6 mice were administered a customized regular diet supplemented with 0.04 % RES for 64 consecutive weeks. Subsequently, the effects of RES on senescent human umbilical vein endothelial cells (HUVECs) induced by H₂O₂ were evaluated. Gene expression analyses were conducted following SIRT1 knockdown in HUVECs treated with H₂O₂ and RES, or transfected with miR-217 mimics and inhibitors. The study found that RES reduced body weight, improved endothelial function, enhanced SIRT1 expression, and suppressed the expression of miR-217, NADPH oxidase 4 (NOX4), and NLRP3 in the senescent thoracic aorta. Additionally, RES significantly reduced the expression of NOX4, X-box binding protein 1 spliced (XBP1s), and reactive oxygen species (ROS) production in a dose-dependent manner in senescent HUVECs. SIRT1 knockdown resulted in the activation of the NLRP3 inflammasome by upregulating NOX4 and XBP1s expression, an effect that was partially attenuated by RES pretreatment. RES also suppressed the expression of miR-217 induced by H₂O₂. The miR-217 mimic facilitated cellular senescence; however, RES mitigated this effect, which was further amplified by the miR-217 inhibitor.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115570"},"PeriodicalIF":4.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199142","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":"Commentary on \"Emodin delays rheumatoid arthritis progression by inhibiting the ROS/ TXNIP/NLRP3 signaling pathway\".","authors":"Xin-Yu Li, Feng-Yi Mai, Jie Guo, Chen-Guang Li","doi":"10.1016/j.intimp.2025.115616","DOIUrl":"https://doi.org/10.1016/j.intimp.2025.115616","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"115616"},"PeriodicalIF":4.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199145","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":"TLR2/NF-κB signaling could oversee the function of CD56bright NK cells in patients afflicted with severe fever and thrombocytopenia syndrome (SFTS)","authors":"Meng-Meng Li ,&nbsp;Hao-Ran Yue ,&nbsp;Jing Wang ,&nbsp;Yan Xiong ,&nbsp;Ming-Bo Cao ,&nbsp;Le-Le Liu","doi":"10.1016/j.intimp.2025.115627","DOIUrl":"10.1016/j.intimp.2025.115627","url":null,"abstract":"<div><div>Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease caused by a novel bunyavirus, presents a significant threat due to its high mortality rate. Immune suppression is recognized as a crucial factor in the progression of this disease. NK cells, as effector cells in the innate immune system, play important immune functions. Toll-like receptors (TLRs), specifically pattern-recognition receptors, initiate the activation of intracellular signaling factors upon activation. However, there is a paucity of data regarding immune responses in SFTS. In this study, we aimed to investigate the changes in TLR2 and NF-κB within NK cells and examine how the TLR2/NF-κB signaling pathway affects NK cells during SFTS. Our findings revealed that in SFTS patients, there was an increase in the expression of TLR2 and NF-κB in both CD56dimCD16+ and CD56brightCD16- NK cell subsets. Additionally, the function of CD56bright NK cells was enhanced in SFTS patients after stimulation with Pam3CSK4. This suggests that TLR2 signaling plays a crucial role in activating and enhancing the function of CD56bright NK cells following SFTS virus infection. This research will facilitate a deeper understanding of the pathogenesis of SFTSV and could provide an immunological foundation for developing new therapeutic strategies.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115627"},"PeriodicalIF":4.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185884","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 \"Paeonol regulates the DDIT4-mTOR signaling pathway in macrophages to promote diabetic wound healing\" [Int. Immunopharmacol. 151 (2025) 114347].","authors":"Kun Li, Yingying Zhang, Yunpeng Diao, Shuyuan Fan","doi":"10.1016/j.intimp.2025.115618","DOIUrl":"https://doi.org/10.1016/j.intimp.2025.115618","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"115618"},"PeriodicalIF":4.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185844","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":"Testosterone as a mediator of APOE4-linked sex differences in Alzheimer's disease","authors":"Zhidan Shi ,&nbsp;Lingzhi Wu ,&nbsp;Chu Zhang ,&nbsp;Xiaoqian Zeng ,&nbsp;Guangzhe Yao ,&nbsp;Xinqi He ,&nbsp;Jiayi Hu ,&nbsp;Tian Xie ,&nbsp;Ling He","doi":"10.1016/j.intimp.2025.115588","DOIUrl":"10.1016/j.intimp.2025.115588","url":null,"abstract":"<div><div>The pathological mechanisms and clinical manifestations of Alzheimer's disease (AD) exhibit significant gender differences, with a higher proportion of female AD patients. Women carrying the apolipoprotein E4 (APOE4) genotype face a markedly higher risk of developing the disease compared to men. APOE4 plays a crucial role in shaping these gender disparities by influencing the characteristic pathologies of AD. As the primary androgen, testosterone and its metabolites play a vital role in maintaining central nervous system homeostasis by interacting with steroid hormone receptors. Testosterone may mediate these effects through the androgen receptor (AR), participate in immune regulation, influence lipid metabolism, and interfere with the cholinergic system, thereby contributing to gender differences among APOE4 carriers. Key regulatory nodes include IL-17 and TGF-β. Furthermore, we synthesized clinical evidence linking testosterone replacement therapy to cognitive impairment, analyzed current research limitations and gaps in the field, and provided theoretical guidance for developing future targeted interventions and gender-specific therapeutic strategies.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115588"},"PeriodicalIF":4.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191675","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":"Kinesin superfamily proteins in cancer: unveiling their role in chemotherapy","authors":"Hamza Abu Owida ,&nbsp;Suleiman Ibrahim Mohammad ,&nbsp;Asokan Vasudevan ,&nbsp;Ashok Kumar Bishoyi ,&nbsp;S. RenukaJyothi ,&nbsp;Rajashree Panigrahi ,&nbsp;Munthar Kadhim Abosaoda ,&nbsp;Gunjan Garg ,&nbsp;Amrita Pargaien","doi":"10.1016/j.intimp.2025.115621","DOIUrl":"10.1016/j.intimp.2025.115621","url":null,"abstract":"<div><div>Kinesin superfamily proteins (KIFs) are driver proteins used by microtubules for intracellular transport, cellular homeostasis, and mitosis. Reportedly, the aberration in the expression of these proteins has been found to mediate sensitivity to chemotherapy. KIF5A, KIF11, and KIF20A are consistently involved in resistance to paclitaxel and docetaxel in breast, lung, and prostate cancers, while KIF14 overexpression is a prognostic marker for poor outcomes in paclitaxel-treated triple-negative breast and cervical cancer. KIF14 and KIF23 in HCC enhance sorafenib and cisplatin resistance, while suppression of KIF5B or KIF20A increases sensitivity to oxaliplatin in colorectal cancer. Clinic-applied fusions of KIF5B with ALK or EGFR have made it possible to use targeted therapy in non-small cell lung cancer. From a mechanistic point of view, PI3K/Akt, JAK/STAT, and NF-κB activation, metabolic reprogramming, and inhibition of cellular programmed death are involved in KIF-mediated resistance. KIF3A or KIF11 silencing increases chemosensitivity, suggesting a dual role here. Present approaches-small-molecule inhibitors, microRNA modulation, and KIF20A peptide vaccines-are hopeful but are beset by issues of toxicity and specificity. Overall, KIFs are context-dependent regulators of chemoresistance and are multifunctional but promising precision oncology targets.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115621"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156821","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":"Synergistic elimination of bacillus Calmette-Guérin biofilm and tissue restoration facilitated by ultrasound-mediated nanoparticles and antioxidants","authors":"Yuqing Zhang ,&nbsp;Chaorong Huang ,&nbsp;Yan Qiu ,&nbsp;Ruicheng Li ,&nbsp;Jialing Liu ,&nbsp;Yonghong Du ,&nbsp;Dairong Li","doi":"10.1016/j.intimp.2025.115582","DOIUrl":"10.1016/j.intimp.2025.115582","url":null,"abstract":"<div><div>Biofilm formation in <em>Mycobacterium tuberculosis</em> (MTB) enhances antibiotic resistance by impeding drug penetration and evading host immunity. This poses a significant challenge to conventional drug therapies, highlighting the urgent need for novel treatment strategies to overcome MTB's biofilm-mediated resistance. This study introduces the development of low-intensity ultrasound-mediated levofloxacin (LEV) and catalase (CAT) -loaded PEG-PLGA nanoparticles (LEV@CAT-NPs) for antimicrobial sonodynamic therapy (aSDT), offering an innovative strategy to combat BCG biofilm infection, by utilizing BCG as a model for MTB. <em>N</em>-acetylcysteine (NAC) was supplemented during the latter stages of the treatment process of anti-infection therapy to facilitate the transformation of macrophages to the M2 phenotype and to promote tissue repair. Ultrasound-mediated LEV@CAT-NPs, along with the subsequent addition of NAC not only enhanced repair at the infection site but also led to a progressive resolution of the inflammatory response in tissues. The treatment regimen induced a shift in macrophage polarization towards the M2 phenotype and modulated cytokine expression, decreasing pro-inflammatory while increasing anti-inflammatory cytokines, which contributed to the restoration of redox balance in the infected tissues. This study proposes a novel therapeutic strategy that not only targets drug-resistant MTB but also promotes tissue repair, highlighting its dual role in infection management.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115582"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156299","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":"Emodin facilitates the transformation of A1/A2 reactive astrocytes through the 11β-HSD1/AKT signaling pathway in the context of cerebral ischemia","authors":"Wenfang Lai ,&nbsp;Huiling Wu ,&nbsp;Yuting Jiang ,&nbsp;Xuerui Zheng ,&nbsp;Jingquan Chen ,&nbsp;Zehao Huang ,&nbsp;Haimian Hong ,&nbsp;Yingzheng Wang ,&nbsp;Wen Xu ,&nbsp;Guizhu Hong ,&nbsp;Ya Lin","doi":"10.1016/j.intimp.2025.115628","DOIUrl":"10.1016/j.intimp.2025.115628","url":null,"abstract":"<div><div>Emodin is the main active ingredient of <em>Rhei Radix et Rhizoma</em>, a herb widely used for ischemic stroke treatment. This study demonstrates for the first time that emodin exerts neuroprotective effects against ischemic stroke by regulating astrocyte phenotypic transformation via the 11β-HSD1/AKT signaling pathway. In rat MCAO and astrocyte/neuron OGD/R models, emodin improved neurological function, reduced infarction volume, and shifted astrocytes from detrimental A1 to beneficial A2 phenotypes. Mechanistically, emodin activated AKT phosphorylation while suppressing the NF-κB pathway (reducing p-IκBα/IκBα and p-p65/p65 ratios). These effects—along with functional improvements—were reversed by AKT inhibitor LY294002. Furthermore, 11β-HSD1 siRNA mimicked emodin's actions in vitro, and supernatants from both emodin- and siRNA-treated astrocytes enhanced neuronal MAP2 expression. These findings identify astrocyte phenotypic modulation via 11β-HSD1/AKT as a key therapeutic mechanism of emodin.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115628"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185856","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}