International immunopharmacology最新文献

{"title":"Corrigendum to \"mTOR aggravated CD4⁺ T cell pyroptosis by regulating the PPARγ-Nrf2 pathway in sepsis\" [Int. Immunopharmacol. 140 (2024) 112822].","authors":"Guoyu Zhao, Yawen Xie, Xianli Lei, Ran Guo, Na Cui","doi":"10.1016/j.intimp.2024.113389","DOIUrl":"10.1016/j.intimp.2024.113389","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"113389"},"PeriodicalIF":4.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464598","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 \"Role of glucose metabolism reprogramming in keratinocytes in the link between psoriasis and metabolic syndrome\" [Int. Immunopharmacol. 139 (2024) 112704].","authors":"Liang Yan, Wenqiu Wang, Yuxin Qiu, Chongli Yu, Rui Wang, Chengxin Li","doi":"10.1016/j.intimp.2024.113384","DOIUrl":"10.1016/j.intimp.2024.113384","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"113384"},"PeriodicalIF":4.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464599","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":"Neuroprotective effects of gypenosides on LPS-induced anxiety and depression-like behaviors.","authors":"Mei Guo, Wen-Jing Pei, Liming Liu, Kexuan Chen, Yong Cheng, Xiang-Lan Piao","doi":"10.1016/j.intimp.2024.113367","DOIUrl":"10.1016/j.intimp.2024.113367","url":null,"abstract":"<p><strong>Aim: </strong>Depression, a prevalent mental disorder, significantly impairs the quality of life and social functioning. Targeting neuroinflammation is a promising therapeutic approach, highlighting the need for natural neuroprotective agents. Gypenosides (Gyp) from Gynostemma pentaphyllum exhibit anxiolytic and antidepressant effects, yet the underlying mechanisms remain unclear. We investigated whether Gyp, isolated and purified by our laboratory, can exert neuroprotective effects by modulating neuroinflammation in the hippocampus and prefrontal cortex (PFC) of mice with LPS-induced anxiety and depression, thereby ameliorating behavioral phenotypes.</p><p><strong>Methods: </strong>LPS (1 mg/kg, i.p.) was used to induce anxiety and depression-like behaviors. Gyp was administered at 50, 100, or 200 mg/kg in pretreatment, with fluoxetine hydrochloride (Flu) as a positive control, for 10 consecutive days.</p><p><strong>Results: </strong>Gyp, especially at 100 mg/kg, significantly ameliorated LPS-induced anxiety and depression in mice, normalizing cytokine expression in the hippocampus and PFC, with IL-1β showing the most pronounced regulation (Hippocampus: Ratio_Gyp-100/LPS = 30.73 %, PFC: Ratio_Gyp-100/LPS = 55.89 %). Gyp also reversed LPS-induced neuronal loss and necrosis, reduced glial cell activation, and prevented the transition of microglia to the M1 phenotype. Mechanistically, Gyp suppressed the activation of the NLRP3 inflammasome in the PFC, and modulated hippocampal synaptic protein loss, thereby mediating neuroinflammation.</p><p><strong>Conclusions: </strong>Gyp improved anxiety and depression in LPS-induced mice, which may be achieved by balancing systemic inflammatory levels, regulating glial cell activation and phenotypic polarization, regulating hippocampal synaptic plasticity, and suppressing the NLRP3/Caspase-1/ASC signaling pathway in the PFC.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"143 Pt 1","pages":"113367"},"PeriodicalIF":4.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464601","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":"Isoamericanin A ameliorates neuronal damage and alleviates vascular cognitive impairments by inhibiting oxidative stress through activation of the Nrf2 pathway.","authors":"Yanqiu Yang, Libin Xu, Xiaohu Yao, Yingjie Wang, Mingxia Fang, Di Zhou, Ning Li, Yue Hou","doi":"10.1016/j.intimp.2024.113366","DOIUrl":"10.1016/j.intimp.2024.113366","url":null,"abstract":"<p><p>Oxidative stress is critically involved in the cognitive dysfunction and neuronal progressive degeneration in the vascular cognitive impairment (VCI). The natural lignan molecular isoamericanin A (ISOA) containing multiple hydroxyl groups has great potential for suppressing oxidative stress in VCI. The primary objective of this study was to delve into the pharmacological properties of ISOA against VCI, as well as to elucidate the mechanisms driving this effect from the perspective of antioxidative stress. Transient bilateral common carotid arteries occlusion (tBCCAO) mice model and hydrogen peroxide (H₂O₂) treated N2a cells were employed in vivo and in vitro, respectively. Behavioral tests showed that ISOA (5, 10 mg/kg) treatment alleviated learning, memorizing, and recognition in tBCCAO model mice. ISOA alleviated the neuronal damages by increasing the number of NeuN-positive cells, decreasing the TUNEL-positive cells density, up-regulating MAP-2 expression, lighting the damage of neuronal nucleus and synapse. Mechanistically, we found that ISOA reduced the oxidative stress in neurons, which manifested by reduction on the expressions of superoxide, H₂O₂, intercellular reactive oxygen species (ROS) and malondialdehyde (MDA) level, and up-regulations on the expressions of anti-oxidant enzymes superoxide dismutase, heme oxygenase-1, glutathione peroxidase 4, glutathione, and NAD(P)H: quinone oxidoreductase 1. Further investigation showed that ISOA activated nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by downregulating the expression of kelch-like ECH-associated protein 1, upregulating the nuclear translocation and expression of Nrf2, and augmenting antioxidant response elements (ARE) promotor activity. The ISOA-mediated promotion on ARE promotor activity and anti-oxidant enzymes expressions, and suppression on superoxide and ROS expressions and MDA levels were weakened by pharmacological inhibition or genetic knockdown of Nrf2. These effects were enhanced after knockdown Keap1 in H₂O₂-treated cells. Our study demonstrates that ISOA alleviates the cognitive impairments and neuronal loss in VCI by attenuating oxidative stress through promoting the activation of Nrf2 pathway.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"143 Pt 1","pages":"113366"},"PeriodicalIF":4.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464600","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 \"Anti-invasive effects of celastrol in hypoxia-induced fibroblast-like synoviocyte through suppressing of HIF-1α/CXCR4 signaling pathway\" [Int. Immunopharmacol. 17(4) (2013) 1028-1036].","authors":"Guo-Qing Li, Dan Liu, Yu Zhang, Ya-Yun Qian, Yao-Dong Zhu, Shi-Yu Guo, Masataka Sunagawa, Tadashi Hisamitsu, Yan-Qing Liu","doi":"10.1016/j.intimp.2024.113266","DOIUrl":"10.1016/j.intimp.2024.113266","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"113266"},"PeriodicalIF":4.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371774","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":"Treadmill exercise improves cerebral ischemia injury by regulating microglia polarization via downregulation of MMP12.","authors":"Song Zhang, Yuanteng Fan, Xiaojian Cao, Chunchu Deng, Jia Xu, Qiuzhi Zhou, Yajie Li, Yatao Yin, Hong Chen","doi":"10.1016/j.intimp.2024.113210","DOIUrl":"10.1016/j.intimp.2024.113210","url":null,"abstract":"<p><strong>Backgroud: </strong>Exercise training is the main strategy for stroke rehabilitation, and it has shown that shifting microglia toward M2 phenotype is beneficial for the recovery of neurological function after stroke. The mechanisms governing exercise training and inflammatory response after cerebral ischemia remain largely unexplored. Herein, the aim of this study was to investigate the role of exercise training in immune response after cerebral ischemia.</p><p><strong>Methods: </strong>The transient middle cerebral artery occlusion (MCAO) rat model and primary microglia under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions were used to mimic the ischemic stroke in vivo and in vitro respectively. Treadmill exercise with gradually increased intensity was initiated the second day after MCAO for a maximum of 14 days. The beam balance test, forelimb placement test, cornering test, modified adhesive removal test were used to assess the behavioral recovery. The right peri-infarct cortex was taken from 3 rats per group for RNA sequencing (RNA-seq) analysis. Real-time PCR, western blot, immunofluorescence, and phagocytosis assay was performed after MCAO and/or OGD/R.</p><p><strong>Results: </strong>Treadmill exercise could significantly improve behavioral outcomes and reduce the infarct volumes. In addition, treadmill exercise switched microglia polarization toward M2 phenotype (Iba⁺/CD206⁺) in the peri-infarct cortex, and significantly increased the levels of anti-inflammatory factors (TGF-β, IL10, Arg-1, CD206) and decreased a pool of pro-inflammatory factors (IL-1β, IL-6, TNF-α, iNOS, CD68) in the peri-infarct areas. RNA-seq analysis and further studies demonstrated that exercise training could significantly reduce the expression of MMP12. Through further immunofluorescence co-labeling analysis, we found that treadmill exercise predominantly reduced the expression of MMP-12 in microglia but not in neuron after MCAO. In primary microglia after OGD/R, MMP12 inhibition switched microglia polarization toward to M2 phenotype, increased the expression of M2 markers, and enhanced its phagocytic capacities.</p><p><strong>Conclusions: </strong>Our data demonstrate that treadmill exercise could improve the inflammatory microenvironment in the brain after ischemic stroke, which may be caused by inhibition of MMP12 expression. MMP12 suppression in primary microglia could remodel microglia immune functions. In summary, this study may provide novel insights into the immune mechanism of exercise training for stroke and suggests potential targets for therapeutic approaches.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"142 Pt B","pages":"113210"},"PeriodicalIF":4.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346122","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 \"Human placental mesenchymal stromal cells modulate IFN-γ and IL-10 secretion by CD4⁺T cells via CD73, and alleviate intestinal damage in mice with graft-versus-host disease\" [Int. Immunopharmacol. 124 (2023) 110767].","authors":"Jiashen Zhang, Yaxuan Zhao, Hengchao Zhang, Kaiyue Han, Junjie Ma, Yanlian Xiong, Guoyan Wang, Xiying Luan","doi":"10.1016/j.intimp.2024.113150","DOIUrl":"10.1016/j.intimp.2024.113150","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"113150"},"PeriodicalIF":4.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286374","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":"Quercetin-primed BMSC-derived extracellular vesicles ameliorate chronic liver damage through miR-136-5p and GNAS/STAT3 signaling pathways.","authors":"Xiaodan Jiang, Zhejun Liu, Hongjie You, Zuoqing Tang, Yun Ma, Ruifang Nie, Zheng Yang, Niancong Che, Wenlan Liu","doi":"10.1016/j.intimp.2024.113162","DOIUrl":"10.1016/j.intimp.2024.113162","url":null,"abstract":"<p><strong>Background: </strong>Chronic liver damage (CLD) is a long-term and progressive liver condition characterized by inflammation, fibrosis, and impaired liver function, which ultimately lead to severe complications such as cirrhosis or liver cancer. Quercetin (Que), a flavonoid in various plants, possesses anti-inflammatory, antiviral, anti-ischemic, and anticancer properties. Recently, extracellular vesicles (EVs) derived from pretreated bone marrow mesenchymal stem cells (BMSCs) have shown immense potential in treating various diseases, including CLD. Thus, this study evaluated the regulatory effects of Que-preconditioned BMSC-derived EVs (Que-EVs) on LPS-stimulated RAW264.7 cells and their therapeutic effects on mice with CLD.</p><p><strong>Methods: </strong>Que-EVs and control-EVs were harvested from the cell culture supernatant of BMSCs. The EVs were characterized using western blot, transmission electron microscopy, and nanoparticle tracking analysis. Further, the DIR labeling of EVs was used to detect in vitro and in vivo uptake. Next, LPS pre-stimulated RAW264.7 cells were treated with Que-EVs and control-EVs for 24 h. The relative expression of inflammatory cytokines and macrophage polarization markers genes was assessed using RT-qPCR, and western blot was conducted to evaluate the GNAS, PI3K, ERK, and STAT3 gene and protein expressions in RAW264.7 cells. Furthermore, transfection techniques were employed to induce miR-136-5p inhibition and GNAS overexpression in RAW264.7 cells to validate the role of miR-136-5p in alleviating inflammation through the GNAS/PI3K/ERK/STAT3 pathway. Subsequently, the outcomes were validated via in vitro experiments.</p><p><strong>Results: </strong>Que enhanced miR-136-5p expression in BMSC-EVs. Furthermore, it was shown that EVs delivered miR-136-5p to macrophages, thereby attenuating M1-type macrophage polarisation through the GNAS/PI3K/ERK/STAT3 pathway, reducing liver inflammation, improving liver function and treating CLD.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"142 Pt B","pages":"113162"},"PeriodicalIF":4.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346101","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":"Trimethylamine N-oxide promotes PERK-mediated endothelial-mesenchymal transition and apoptosis thereby aggravates atherosclerosis.","authors":"Wang Bingyu, Qiu Jun, Liu Bingyang, Yang Xi, Zhou Jianqing, Lian Jiangfang","doi":"10.1016/j.intimp.2024.113209","DOIUrl":"10.1016/j.intimp.2024.113209","url":null,"abstract":"<p><p>The endothelial-mesenchymal transition (EndMT) is involved in the development of atherosclerosis (AS) and is a key process in vascular endothelial injury. Oxidative stress, inflammation, and apoptosis are common causes of EndMT, and EndMT progression can further accelerate the development of AS. The metabolite trimethylamine N-oxide (TMAO) is produced by the gut microbiome and is implicated in the development of several diseases, including diabetes and chronic kidney disease. However, the impact of TMAO on transforming growth factor β1(TGF-β1)-induced EndMT remains unclear. We hypothesize that TMAO exacerbates plaque formation and cardiac function impairment by promoting EndMT. Herein, we showed that high serum TMAO levels caused plaque formation, cardiac function damage and haemodynamic changes in ApoE^-/- mice. In vitro, TMAO upregulated mesenchymal markers and downregulated endothelial markers in HAECs. Furthermore, TMAO increased the migratory capacity of EndMT cells. Mechanistically, we found that PERK downregulation could alleviate TMAO-induced oxidative stress, EndMT, plaque formation and cardiac function damage. Further study showed that activated transcription factor 3 (ATF3), the downstream molecule of protein kinase RNA-like endoplasmic reticulum kinase (PERK), could bind with TGF-β1/2 and affect EndMT. Overall, TMAO promotes EndMT, possibly through the PERK-eIF2α-ATF4-CHOP or the PERk-eIF2α-ATF3-TGF-β signalling pathways.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"142 Pt B","pages":"113209"},"PeriodicalIF":4.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346123","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":"Liraglutide alleviates ferroptosis in renal ischemia reperfusion injury via inhibiting macrophage extracellular trap formation.","authors":"Zejia Sun, Feilong Zhang, Zihao Gao, Jiyue Wu, Qing Bi, Xiang Zheng, Jiandong Zhang, Peng Cao, Wei Wang","doi":"10.1016/j.intimp.2024.113258","DOIUrl":"10.1016/j.intimp.2024.113258","url":null,"abstract":"<p><strong>Background and purpose: </strong>Renal transplantation and other conditions with transiently reduced blood flow is major cause of renal ischemia/reperfusion injury (RIRI), a therapeutic challenge clinically. This study investigated the role of liraglutide in ferroptosis-associated RIRI via macrophage extracellular traps (METs).</p><p><strong>Methods: </strong>Animal model with RIRI was established in C57BL/6J mice. A total of 72 C57BL/6J mice were used with 8 mice per group. Primary tubular epithelium was co-culture with RAW264.7 under hypoxia/reoxygenation (H/R) condition to mimic in vitro. Liraglutide was administrated into mice and cells. Extracellular DNA, neutrophil elastase and myeloperoxidase in serum and supernatant of cell medium were collected for measuring METs. F4/80 and citH3 were labeled to show METs.</p><p><strong>Results: </strong>Liraglutide relieved RIRI and ferroptosis in vivo, and inhibited renal I/R-induced METs both in vivo and in vitro. F4/80 and citrullinated histone H3 (citH3) were highly co-localized after RIRI. Liraglutide attenuated the co-localization of citH3 and F4/80. Expressions of M2 markers were enhanced whereas these of M1 markers suppressed during liraglutide treatment in RIRI. Phosphorylation of signal transducer and activator of transcription (STAT)1, 3 and 6 were increased in RIRI mice and H/R-induced RAW264.7. However, liraglutide decreased phosphorylation of STAT1 and increased phosphorylation of STAT3 and STAT6. STAT3/6 inhibition reversed liraglutide-inhibited M1 polarization, extracellular traps and ferroptosis.</p><p><strong>Conclusion: </strong>Liraglutide inhibited ferroptosis-induced renal dysfunction since it skewed macrophage polarization into M2 phenotype that interfered the formation of extracellular traps based on STAT3/6 pathway during RIRI. Liraglutide was proposed to be used for RIRI clinical treatment.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"142 Pt B","pages":"113258"},"PeriodicalIF":4.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346098","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}