Immunobiology最新文献

{"title":"Acute lung injury is prevented by monocyte locomotion inhibitory factor in an experimental severe malaria mouse model","authors":"Martha Jackeline Pérez-Vega ,&nbsp;Gerardo Manuel Corral-Ruiz ,&nbsp;Adrian Galán-Salinas ,&nbsp;Raúl Silva-García ,&nbsp;Ismael Mancilla-Herrera ,&nbsp;Jorge Barrios-Payán ,&nbsp;Luis Fabila-Castillo ,&nbsp;Rogelio Hernández-Pando ,&nbsp;Luvia Enid Sánchez-Torres","doi":"10.1016/j.imbio.2024.152823","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152823","url":null,"abstract":"<div><p>Acute lung injury caused by severe malaria (SM) is triggered by a dysregulated immune response towards the infection with <em>Plasmodium</em> parasites. Postmortem analysis of human lungs shows diffuse alveolar damage (DAD), the presence of CD8 lymphocytes, neutrophils, and increased expression of Intercellular Adhesion Molecule 1 (ICAM-1). <em>P. berghei</em> ANKA (<em>Pb</em>A) infection in C57BL/6 mice reproduces many SM features, including acute lung injury characterized by DAD, CD8⁺ T lymphocytes and neutrophils in the lung parenchyma, and tissular expression of proinflammatory cytokines and adhesion molecules, such as IFNγ, TNFα, ICAM, and VCAM. Since this is related to a dysregulated immune response, immunomodulatory agents are proposed to reduce the complications of SM. The monocyte locomotion inhibitory factor (MLIF) is an immunomodulatory pentapeptide isolated from axenic cultures of <em>Entamoeba hystolitica.</em> Thus, we evaluated if the MLIF intraperitoneal (i.p.) treatment prevented SM-induced acute lung injury. The peptide prevented SM without a parasiticidal effect, indicating that its protective effect was related to modifications in the immune response. Furthermore, peripheral CD8⁺ leukocytes and neutrophil proportions were higher in infected treated mice. However, the treatment prevented DAD, CD8⁺ cell infiltration into the pulmonary tissue and downregulated IFNγ. Moreover, VCAM-1 expression was abrogated. These results indicate that the MLIF treatment downregulated adhesion molecule expression, impeding cell migration and proinflammatory cytokine tissular production, preventing acute lung injury induced by SM. Our findings represent a potential novel strategy to avoid this complication in various events where a dysregulated immune response triggers lung injury.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 4","pages":"Article 152823"},"PeriodicalIF":2.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017129852400041X/pdfft?md5=26319187ec811414fa1737f8bf61030f&pid=1-s2.0-S017129852400041X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOE expression in papillary thyroid carcinoma: Influencing tumor progression and macrophage polarization","authors":"Ronghua Huo ,&nbsp;Ruhua Zhao ,&nbsp;Ziwen Li ,&nbsp;Min Li ,&nbsp;Yu Bin ,&nbsp;Dongmei Wang ,&nbsp;Gang Xue ,&nbsp;Jingfang Wu ,&nbsp;Xu Lin","doi":"10.1016/j.imbio.2024.152821","DOIUrl":"10.1016/j.imbio.2024.152821","url":null,"abstract":"<div><h3>Background</h3><p>As metastatic papillary thyroid carcinoma becomes increasingly challenging to treat, immunotherapy has emerged as a new research direction. Tumor-associated macrophages (TAMs) influence the occurrence, invasion, and metastasis of tumors. Apolipoprotein E (APOE) can regulate the polarization changes of macrophages and participate in the remodeling of the tumor microenvironment. However, the role of APOE in regulating the polarization and biological functions of TAMs in papillary thyroid carcinoma (PTC) remains unclear, as it acts as a dual biomarker.</p></div><div><h3>Methods</h3><p>We probed APOE expression in PTC tissues using immunohistochemical staining. A cell co-culture model was established where different APOE-expressing K1 cells were co-cultured with THP-1-derived M0 macrophages. An in-depth analysis of macrophage polarization behavior was performed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Subsequently, the impact of APOE-regulated macrophages on tumor cell behavior, especially proliferation, migration, and invasion, was evaluated utilizing IncuCyte ZOOM system, flow cytometry, colony formation, and scratch experiments. Finally, we used a xenograft model to confirm the effects of APOE on PTC tumorigenesis.</p></div><div><h3>Results</h3><p>Tumor dimensions, stage, and lymphatic metastases were significantly associated with increased APOE expression in PTC tissues. K1 cells were markedly limited in their proliferation, migration, and invasion abilities when APOE expression was silenced, a process mediated by the PI3K/Akt/NF-κB signaling axis. Moreover, APOE is a key facilitator of the enhancement of the anti-inflammatory cytokines IL-10 and TGF-β1. In PTC cellular models, APOE contributed to the phenotypic shift of THP-1 derived macrophages towards an M2 phenotypic polarization, predominantly through the modulation of IL-10. Furthermore, in vivo studies involving athymic nude mice have demonstrated pivotal role of APOE in tumor progression and the induction of M2-like TAM polarization.</p></div><div><h3>Conclusion</h3><p>Our results elucidated that APOE could promote the shift of TAMs from M0-type to M2-type polarization by regulating inflammatory factors expressions in K1 cell through the PI3K/Akt/NF-κB pathway. These findings are crucial for understanding the molecular mechanisms underlying PTC pathogenesis and for developing immunological drugs to treat this disease.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152821"},"PeriodicalIF":2.5,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000391/pdfft?md5=8a66ffb600ffb24e81930d94c9b0f7e5&pid=1-s2.0-S0171298524000391-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141407760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the dynamic transcriptional landscape of Treg subpopulations in pancreatic ductal adenocarcinoma: Insights from single-cell RNA sequencing analysis with a focus on CTLA4 and TIGIT","authors":"Adib Miraki Feriz ,&nbsp;Arezou Khosrojerdi ,&nbsp;Nafiseh Erfanian ,&nbsp;Setareh Azarkar ,&nbsp;Seyed Mehdi Sajjadi ,&nbsp;Mohammad Javad Shojaei ,&nbsp;Mohammad Javad Vaferi ,&nbsp;Hossein Safarpour ,&nbsp;Vito Racanelli","doi":"10.1016/j.imbio.2024.152822","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152822","url":null,"abstract":"<div><p>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy that represents a significant challenge in cancer research and clinical management. In this study, we reanalyzed a published single-cell RNA sequencing (scRNA-seq) dataset from PDAC and adjacent tissues to investigate the heterogeneity of tumor and normal tissue, specifically focusing on the regulatory T cells (Tregs) and their interactions with other cells in the tumor microenvironment (TME). Treg cells were identified and clustered into natural Tregs (nTreg) and induced Tregs (iTreg) based on the expression of specific genes. It was found that the number of iTregs was higher in the tumor than in healthy tissues, while the number of n Tregs was higher in healthy tissues. Differential gene expression analysis was performed, and biological process analysis revealed that the Tregs in PDAC were mostly involved in protein targeting and translation pathways. In addition, ligand-receptor pairs between Tregs and other cell types were identified, and the critical communication pathways between Tregs and endothelial and ductal cells were revealed, which could potentially contribute to the immunosuppressive TME of PDAC. These findings provide insights into the role of Tregs in PDAC and their interactions with other cell types in the TME, highlighting potential targets for immunotherapy, such as the inhibitory immune checkpoint receptors CTLA4 and TIGIT, which are known to be expressed on Tregs and have been shown to play a role in suppressing anti-tumor immune responses.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 4","pages":"Article 152822"},"PeriodicalIF":2.8,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000408/pdfft?md5=7ab292ccc8ea385fe038100ea6310ef4&pid=1-s2.0-S0171298524000408-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141291975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variations in the interferon and TLR3 genes may be associated with susceptibility to systemic lupus erythematosus and its clinical presentation","authors":"E. Modzelewska ,&nbsp;A. Wajda ,&nbsp;A. Lutkowska ,&nbsp;A. Felis-Giemza ,&nbsp;B. Stypińska ,&nbsp;A. Matusiewicz ,&nbsp;M. Puszczewicz ,&nbsp;D. Majewski ,&nbsp;P.P. Jagodziński ,&nbsp;E. Haładyj ,&nbsp;A. Paradowska-Gorycka","doi":"10.1016/j.imbio.2024.152807","DOIUrl":"10.1016/j.imbio.2024.152807","url":null,"abstract":"<div><p>The study aimed to explore the pontential impact of 10 polymorphisms within <em>IFN-α</em>, <em>IFN-β1</em>, <em>IFN-γ</em> and <em>TLR3</em> genes on SLE phenotype and susceptibility and to study the relationship between specific genotypes and clinics. Whole blood samples from SLE patients and healthy controls was obtained. DNA was extracted from the peripheral blood by the QIAamp DNA Blood Mini Kit (Qiagen). The quality and quantity of isolated DNA was estimated by the Quawell Q5000 spectrophotometer. We genotyped SLE patients and healthy subjects using real-time PCR (QuantStudio 5 thermocycler). The study suggests that <em>IFN-γ</em> rs2069705, <em>IFN-γ</em> rs2069718 and <em>IFN-α</em> rs3758236 polymorphisms have a protective role in SLE. We observed relations between <em>TLR3</em> rs3775292, <em>IFN-β1</em> rs7873167, <em>IFN-γ</em> rs2069705, <em>TLR3</em> rs3775291 and <em>TLR3</em> rs5743305 polymorphisms and clinical picture of SLE patients. We found associations between the <em>IFN-α</em> rs3758236, <em>IFN-γ</em> rs2069705, <em>IFN-γ</em> rs2069718, <em>IFN-γ</em> rs1861493 and <em>IFN-β1</em> rs10964831 polymorphisms and the clinical manifestation of the SLE and/or its comorbidities. We perceived links between <em>IFN-γ</em> rs2069705, <em>IFN-γ</em> rs2069718, <em>IFN-γ</em> rs1861493, <em>TLR3</em> rs3775291, <em>TLR3</em> rs3775292 and <em>TLR3</em> rs5743305 polymorphisms and the occurrence of autoantibodies. Our study presented the relationship between IFN and TLR gene polymorphisms with SLE susceptibility, phenotype and autoantibodies profile. This study propose that polymorphisms within interferons and TLR3 genes can be engaged in the SLE pathogenesis and course.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 4","pages":"Article 152807"},"PeriodicalIF":2.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000251/pdfft?md5=c319ca0f2f1222e8633292a0bb1a8ecf&pid=1-s2.0-S0171298524000251-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered serum concentrations of IL-8, IL-32 and IL-10 in patients with lung impairment 6 months after COVID-19","authors":"Laura Bergantini,&nbsp;Sara Gangi,&nbsp;Miriana d’Alessandro,&nbsp;Paolo Cameli,&nbsp;Beatrice Perea,&nbsp;Martina Meocci,&nbsp;Gaia Fabbri,&nbsp;Francesco Bianchi,&nbsp;Elena Bargagli","doi":"10.1016/j.imbio.2024.152813","DOIUrl":"10.1016/j.imbio.2024.152813","url":null,"abstract":"<div><p>Post-COVID symptoms are reported in 10–35 % of patients not requiring hospitalization, and in up to 80 % of hospitalized patients and patients with severe disease. The pathogenesis of post-COVID syndrome remains largely unknown. Some evidence suggests that prolonged inflammation has a key role in the pathogenesis of most post-COVID manifestations. We evaluated a panel of inflammatory and immune-mediated cytokines in individuals with altered HRCT features and in patients without any long-term COVID symptoms. Blood samples of 89 adult patients previously hospitalized with COVID-19 were collected and stratified as patients with and without HRCT evidence of fibrotic lung alterations. Serum analyte concentrations of IL-4, IL-2, CXCL10 (IP-10), IL-1β, TNF-α, CCL2 (MCP-1), IL-17A, IL-6, IL-10, IFN-γ, IL-12p70 and TGF-β1 (free active form) were quantified by bead-based multiplex assay. Clinical and functional data were recorded in a database.</p><p>With the use of machine learning approach, IL-32, IL-8, and IL-10 proved to be associated with the development of HRCT evidence of lung sequelae at follow-up. Direct comparison of cytokine levels in the two groups showed increased levels of IL-32 and decreased levels of IL-8 in patients with lung impairment. After further stratification of patients by severity (severe versus mild/moderate) during hospitalization, IL-10 emerged as the only cytokine showing decreased levels in severe patients. These findings contribute to a better understanding of the immune response and potential prognostic markers in patients with lung sequelae after COVID-19.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 4","pages":"Article 152813"},"PeriodicalIF":2.8,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000317/pdfft?md5=ef9af97e3922b78587ba4d6233126d7b&pid=1-s2.0-S0171298524000317-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141145153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptome analysis of macrophage subpopulations contributing to chemotherapy resistance in ovarian cancer","authors":"Xiaolin Zhong ,&nbsp;Fei Zhang ,&nbsp;Hongyang Xiao ,&nbsp;Ruiqing Tu","doi":"10.1016/j.imbio.2024.152811","DOIUrl":"10.1016/j.imbio.2024.152811","url":null,"abstract":"<div><h3>Background</h3><p>Ovarian cancer, a fatal gynecological malignancy, is primarily managed through surgery and chemotherapy. However, a significant challenge arises as patients frequently experience relapse due to chemotherapy resistance. This study delves into the complex functions and underlying mechanisms of macrophages in chemotherapy resistance in ovarian cancer.</p></div><div><h3>Method</h3><p>The single-cell transcriptome sequencing data of ovarian cancer with or without chemotherapy were analyzed. Then, corresponding cell types were identified, and macrophages were extracted from all cells. Following the standardized single-cell analysis using the Seurat package, 15 distinct macrophage clusters were found and differentially expressed genes among them were analyzed. Moreover, their association with chemotherapy resistance was explored through cell proportions and gene expression.</p></div><div><h3>Result</h3><p>In the single-cell transcriptomic analysis of ovarian cancer tissues before and after chemotherapy, the cellular proportion of CXCL5⁺ macrophages, THBS1⁺ macrophages, and MMP9⁺ macrophages were significantly increased following chemotherapy. Further investigation revealed that these macrophage subpopulations upregulated the expression of multiple pro-tumorigenic angiogenic or invasive factors, in addition to CXCL5, THBS1, and MMP9, including CTSL, CXCL1, and CCL18. Finally, pathway enrichment analysis revealed the significant activation of signaling pathways, such as NOD-like receptor, MAPK, and TNF in these macrophage subpopulations, which provides direction for studying the mechanism of these subpopulations.</p></div><div><h3>Conclusion</h3><p>CXCL5⁺, THBS1⁺, and MMP9⁺ macrophage subpopulations exhibit an increased cellular prevalence post-chemotherapy and pro-tumorigenic molecular expression profiles, suggesting a close association with chemoresistance in ovarian cancer. These findings contribute to our understanding of the roles and mechanisms of macrophages in ovarian cancer chemoresistance, providing a theoretical basis and direction for the development of therapies targeting macrophages in overcoming ovarian cancer chemoresistance.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152811"},"PeriodicalIF":2.5,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000299/pdfft?md5=16a380283ad6102df75ef62fc7b99dbe&pid=1-s2.0-S0171298524000299-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141133235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the cGAS-STING pathway by viral dsDNA leading to M1 polarization of macrophages mediates antiviral activity against hepatitis B virus","authors":"Qiyin Zong ,&nbsp;Hao Zhang ,&nbsp;Futing Liu ,&nbsp;Jianfei Li ,&nbsp;Qian Liu ,&nbsp;Zhi Duan ,&nbsp;Wanlu Duan ,&nbsp;Mengqi Ruan ,&nbsp;Jingjing Zhang ,&nbsp;Yan Liu ,&nbsp;Qiang Zhou ,&nbsp;Qin Wang","doi":"10.1016/j.imbio.2024.152810","DOIUrl":"10.1016/j.imbio.2024.152810","url":null,"abstract":"<div><h3>Background and aims</h3><p>Activation of the cGAS-STING pathway induces the production of type I interferons, initiating the antiviral immune response, which contributes to the clearance of pathogens. Previous studies have shown that STING agonists promote hepatitis B virus (HBV) clearance; however, few studies have investigated the effect of activating the cGAS-STING pathway in macrophages on HBV.</p></div><div><h3>Methods</h3><p>The polarization status of HBV particle-stimulated RAW264.7 macrophages was analyzed. After stimulation with HBV particles, the analysis focused on determining whether the DNA sensors in RAW264.7 macrophages recognized the viral double-stranded DNA (dsDNA) and evaluating the activation of the cGAS-STING pathway. Coculture of mouse macrophages and hepatocytes harboring HBV was used to study the antiviral activity of HBV-stimulated RAW264.7 macrophages.</p></div><div><h3>Results</h3><p>After stimulation with HBV particles, HBV relaxed circular DNA (rcDNA) was detected in RAW264.7 macrophages, and the protein expression of phospho-STING, phospho-TBK1, and phospho-IRF3 in the STING pathway was increased, as shown by Western blot analysis, which revealed that M1 polarization of macrophages was caused by increased expression of CD86. RT–PCR analyses revealed elevated expression of M1 macrophage polarization-associated cytokines such as TNFα, IL-1β, iNOS, and IFNα/β. In the coculture experiment, both HBsAg and HBeAg expression levels were significantly decreased in AML12-HBV1.3 cells cocultured with the supernatants of HBV-stimulated RAW264.7 macrophages.</p></div><div><h3>Conclusion</h3><p>The results suggest that macrophages can endocytose HBV particles. Additionally, viral dsDNA can be recognized by DNA pattern recognition receptors, which in turn activate the cGAS-STING pathway, promoting the M1 polarization of macrophages, while no significant M2 polarization is observed. Macrophages stimulated with HBV particles exhibit enhanced antiviral activity against HBV.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152810"},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000287/pdfft?md5=3e9abaec68e88266eb8af05ce306528c&pid=1-s2.0-S0171298524000287-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141023275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The involvement of oxidative stress and the TLR4/NF-κB/NLRP3 pathway in acute lung injury induced by high-altitude hypoxia","authors":"Wangjie Cao ,&nbsp;Yuanding Zeng ,&nbsp;Yun Su ,&nbsp;Hongxia Gong ,&nbsp;Jianzheng He ,&nbsp;Yongqi Liu ,&nbsp;Congyi Li","doi":"10.1016/j.imbio.2024.152809","DOIUrl":"10.1016/j.imbio.2024.152809","url":null,"abstract":"<div><h3>Objective</h3><p>This study investigated the effect of oxidative stress and the TLR4/NF-κB/NLRP3 pathway on the pathogenesis of acute lung injury (ALI) induced by high-altitude hypoxia.</p></div><div><h3>Methods</h3><p>Rats were placed in an animal hyperbaric oxygen chamber to establish a rat model of ALI induced by high-altitude hypoxia after treatment with N-acetylcysteine (NAC; a reactive oxygen species [ROS] inhibitor) or/and MCC950 (an NLPR3 inflammasome inhibitor). After modeling, the wet-to-dry weight ratio (W/D) of rat lung tissues was calculated. In lung tissues, ROS levels were detected with immunofluorescence, the enzyme activity was tested with the kit, and the expression of TLR4/NF-κB/NLRP3 pathway-related genes and proteins was measured with western blotting and qRT-PCR. The levels of inflammatory factors in the serum were quantified with ELISA.</p></div><div><h3>Results</h3><p>After modeling, rats showed significantly increased W/D, ROS levels, and Malondialdehyde (MDA) concentrations and markedly diminished Superoxide dismutase (SOD) and Glutathione (GSH) concentrations in lung tissues (all <em>P</em> &lt; 0.01), accompanied by substantially enhanced serum levels of TNF-α, IL-6, and IL-1β, significantly reduced serum levels of IL-10, and remarkably augmented TLR4, NLRP3, p-NF-κB p65, NF-κB p65 mRNA, and Caspase-1 expression in lung tissues (all <em>P</em> &lt; 0.01). Furthermore, treatment with NAC or MCC950 alone or in combination prominently lowered the W/D of lung tissues (<em>P</em> &lt; 0.01), serum levels of TNF-α (<em>P</em> &lt; 0.05), IL-6 (<em>P</em> &lt; 0.05), and IL-1β (<em>P</em> &lt; 0.01), and NF-κB p65 expression and phosphorylation (<em>P</em> &lt; 0.05, <em>P</em> &lt; 0.01) while significantly increasing SOD and GSH concentrations (<em>P</em> &lt; 0.05, <em>P</em> &lt; 0.01) and serum levels of IL-10 (<em>P</em> &lt; 0.01) in modeled rats. Meanwhile, treatment of NAC alone or combined with MCC950 significantly reduced MDA concentration and ROS levels (<em>P</em> &lt; 0.05, <em>P</em> &lt; 0.01) in modeled rats, and treatment of MCC950 alone or combined with NAC considerably declined TLR4, NLRP3, and Caspase-1 expression in modeled rats (<em>P</em> &lt; 0.05, <em>P</em> &lt; 0.01).</p></div><div><h3>Conclusion</h3><p>Inhibition of oxidative stress and the TLR4/NF-κB/NLRP3 pathway can ameliorate ALI in rats exposed to high-altitude hypoxia.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152809"},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000275/pdfft?md5=f25edf5c948cf75bef00c87105c842c3&pid=1-s2.0-S0171298524000275-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141053838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antipyretic and anti-inflammatory effects of inosine, an active component of Kangfuxin","authors":"Yue Zhang ,&nbsp;Daqi Jia ,&nbsp;Yipeng Wu ,&nbsp;Yongqing Xu","doi":"10.1016/j.imbio.2024.152812","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152812","url":null,"abstract":"<div><p>Kangfuxin has been widely recognized for its use in treating ulcerative conditions and mucositis, primarily due to its anti-inflammatory properties, which promote cell proliferation, granulation tissue growth, and angiogenesis. However, the exact mechanisms underlying these effects remain poorly understood. In this study, we employed high-throughput mass spectrometry to identify 11 compounds in Kangfuxin, including uracil, hypoxanthine, xanthine, inosine, glutamic acid, glycine, alanine, valine, isoleucine, leucine, and lysine. Notably, the antipyretic and anti-inflammatory properties of inosine, one of these compounds, have not been well characterized. To address this gap, we induced fever in vivo using lipopolysaccharide (LPS) and conducted various experiments, including the analysis of endogenous mediators, inflammatory factors, quantitative polymerase chain reaction (QPCR), Western blotting, and hematoxylin and eosin (HE) staining. Our findings indicate that inosine significantly reduces LPS-induced fever, inhibits the expression of inflammatory factors, and alleviates the inflammatory response. These results suggest that inosine may serve as a potential therapeutic target for inflammatory diseases.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152812"},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000305/pdfft?md5=a0a9daf915cdcdab7fe546ec0fd73801&pid=1-s2.0-S0171298524000305-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141083215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD” [Immunobiology 217/3 (2012) 345–353]","authors":"Mirella Profita ,&nbsp;Loredana Riccobono ,&nbsp;Angela Marina Montalbano ,&nbsp;Anna Bonanno ,&nbsp;Maria Ferraro ,&nbsp;Giusy Daniela Albano ,&nbsp;Stefania Gerbino ,&nbsp;Paola Casarosa ,&nbsp;Michael Paul Pieper ,&nbsp;Mark Gjomarkaj","doi":"10.1016/j.imbio.2024.152800","DOIUrl":"10.1016/j.imbio.2024.152800","url":null,"abstract":"","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152800"},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000184/pdfft?md5=eb7474231d69bfc5afc258b8a5a9fff9&pid=1-s2.0-S0171298524000184-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}