Inflammation Research最新文献

{"title":"A single dose of angiotensin-(1–7) resolves eosinophilic inflammation and protects the lungs from a secondary inflammatory challenge","authors":"Giselle Santos Magalhaes, Juliana Fabiana Gregorio, Vinicius Amorim Beltrami, Franciel Batista Felix, Livia Oliveira-Campos, Caio Santos Bonilha, Renato Fraga Righetti, Iolanda de Fátima Lopes Calvo Tibério, Frederico B. De Sousa, Barbara Maximino Rezende, Andréa Teixeira-Carvalho, Robson AS Santos, Maria José Campagnole-Santos, Maria da Gloria Rodrigues-Machado, Mauro Martins Teixeira, Vanessa Pinho","doi":"10.1007/s00011-024-01880-x","DOIUrl":"https://doi.org/10.1007/s00011-024-01880-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Angiotensin-(1–7) [Ang-(1–7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1–7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1–7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Treatment with Ang-(1–7) resulted in elevated levels of IL-10, CD4⁺Foxp3⁺, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1–7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1–7) effectively prevented the lung inflammation.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>A single dose of Ang-(1–7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140802917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor necrosis factor receptor-associated factor 5 protects against intimal hyperplasia by regulation of macrophage polarization via directly targeting PPARγ","authors":"Wen-Lin Cheng, Sheng-ping Chao, Fang Zhao, Huan-Huan Cai, Ziyue Zeng, Jian-Lei Cao, Zhili Jin, Ke-Qiong Deng, Xiaorong Hu, Hairong Wang, Zhibing Lu","doi":"10.1007/s00011-024-01875-8","DOIUrl":"https://doi.org/10.1007/s00011-024-01875-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>Intimal hyperplasia is a serious clinical problem associated with the failure of therapeutic methods in multiple atherosclerosis-related coronary heart diseases, which are initiated and aggravated by the polarization of infiltrating macrophages. The present study aimed to determine the effect and underlying mechanism by which tumor necrosis factor receptor-associated factor 5 (TRAF5) regulates macrophage polarization during intimal hyperplasia.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>TRAF5 expression was detected in mouse carotid arteries subjected to wire injury. Bone marrow-derived macrophages, mouse peritoneal macrophages and human myeloid leukemia mononuclear cells were also used to test the expression of TRAF5 in vitro. Bone marrow-derived macrophages upon to LPS or IL-4 stimulation were performed to examine the effect of TRAF5 on macrophage polarization. TRAF5-knockout mice were used to evaluate the effect of TRAF5 on intimal hyperplasia.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>TRAF5 expression gradually decreased during neointima formation in carotid arteries in a time-dependent manner. In addition, the results showed that TRAF5 expression was reduced in classically polarized macrophages (M1) subjected to LPS stimulation but was increased in alternatively polarized macrophages (M2) in response to IL-4 administration, and these changes were demonstrated in three different types of macrophages. An in vitro loss-of-function study with TRAF5 knockdown plasmids or TRAF5-knockout mice revealed high expression of markers associated with M1 macrophages and reduced expression of genes related to M2 macrophages. Subsequently, we incubated vascular smooth muscle cells with conditioned medium of polarized macrophages in which TRAF5 expression had been downregulated or ablated, which promoted the proliferation, migration and dedifferentiation of VSMCs. Mechanistically, TRAF5 knockdown inhibited the activation of anti-inflammatory M2 macrophages by directly inhibiting PPARγ expression. More importantly, TRAF5-deficient mice showed significantly aggressive intimal hyperplasia.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Collectively, this evidence reveals an important role of TRAF5 in the development of intimal hyperplasia through the regulation of macrophage polarization, which provides a promising target for arterial restenosis-related disease management.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PLD2 deletion ameliorates sepsis-induced cardiomyopathy by suppressing cardiomyocyte pyroptosis via the NLRP3/caspase 1/GSDMD pathway","authors":"Jun Li, Da Teng, Wenjuan Jia, Lei Gong, Haibin Dong, Chunxiao Wang, Lihui Zhang, Bowen Xu, Wenlong Wang, Lin Zhong, Jianxun Wang, Jun Yang","doi":"10.1007/s00011-024-01881-w","DOIUrl":"https://doi.org/10.1007/s00011-024-01881-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication. Phospholipase D2 (PLD2) is crucial in mediating inflammatory reactions and is associated with the prognosis of patients with sepsis. Whether PLD2 is involved in the pathophysiology of SICM remains unknown. This study aimed to investigate the effect of PLD2 knockout on SICM and to explore potential mechanisms.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The SICM model was established using cecal ligation and puncture in wild-type and PLD2-knockout mice and lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Transfection with PLD2-shRNA lentivirus and a PLD2 overexpression plasmid were used to interfere with PLD2 expression in H9C2 cells. Cardiac pathological alterations, cardiac function, markers of myocardial injury, and inflammatory factors were used to evaluate the SICM model. The expression of pyroptosis-related proteins (NLRP3, cleaved caspase 1, and GSDMD-N) was assessed using western blotting, immunofluorescence, and immunohistochemistry.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>SICM mice had myocardial tissue damage, increased inflammatory response, and impaired heart function, accompanied by elevated PLD2 expression. PLD2 deletion improved cardiac histological changes, mitigated cTNI production, and enhanced the survival of the SICM mice. Compared with controls, PLD2-knockdown H9C2 exhibits a decrease in inflammatory markers and lactate dehydrogenase production, and scanning electron microscopy results suggest that pyroptosis may be involved. The overexpression of PLD2 increased the expression of NLRP3 in cardiomyocytes. In addition, PLD2 deletion decreased the expression of pyroptosis-related proteins in SICM mice and LPS-induced H9C2 cells.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>PLD2 deletion is involved in SICM pathogenesis and is associated with the inhibition of the myocardial inflammatory response and pyroptosis through the NLRP3/caspase 1/GSDMD pathway.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viperin inhibits interferon-γ production to promote Mycobacterium tuberculosis survival by disrupting TBK1-IKKε-IRF3-axis and JAK-STAT signaling","authors":"Yao Liang, Yun Liang, Qi Wang, Qianna Li, Yingqi Huang, Rong Li, Xiaoxin Pan, Linmiao Lie, Hui Xu, Zhenyu Han, Honglin Liu, Qian Wen, Chaoying Zhou, Li Ma, Xinying Zhou","doi":"10.1007/s00011-024-01873-w","DOIUrl":"https://doi.org/10.1007/s00011-024-01873-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objectives and design</h3><p>As an interferon-inducible protein, Viperin has broad-spectrum antiviral effects and regulation of host immune responses. We aim to investigate how Viperin regulates interferon-γ (IFN-γ) production in macrophages to control <i>Mycobacterium tuberculosis</i> (Mtb) infection.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We use Viperin deficient bone-marrow-derived macrophage (BMDM) to investigate the effects and machines of Viperin on Mtb infection.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Viperin inhibited IFN-γ production in macrophages and in the lung of mice to promote Mtb survival. Further insight into the mechanisms of Viperin-mediated regulation of IFN-γ production revealed the role of TANK-binding kinase 1 (TBK1), the TAK1-dependent inhibition of NF-kappa B kinase-epsilon (IKKε), and interferon regulatory factor 3 (IRF3). Inhibition of the TBK1-IKKε-IRF3 axis restored IFN-γ production reduced by Viperin knockout in BMDM and suppressed intracellular Mtb survival. Moreover, Viperin deficiency activated the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, which promoted IFN-γ production and inhibited Mtb infection in BMDM. Additionally, a combination of the anti-TB drug INH treatment in the absence of Viperin resulted in further IFN-γ production and anti-TB effect.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This study highlights the involvement of TBK1-IKKε-IRF3 axis and JAK-STAT signaling pathways in Viperin-suppressed IFN-γ production in Mtb infected macrophages, and identifies a novel mechanism of Viperin on negatively regulating host immune response to Mtb infection.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of multiomics analyses reveals unique insights into CD24-mediated immunosuppressive tumor microenvironment of breast cancer","authors":"Haihong Hu, Hongxia Zhu, Wendi Zhan, Bo Hao, Ting Yan, Jingdi Zhang, Siyu Wang, Xuefeng Xu, Taolan Zhang","doi":"10.1007/s00011-024-01882-9","DOIUrl":"https://doi.org/10.1007/s00011-024-01882-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Tumor immunotherapy brings new light and vitality to breast cancer patients, but low response rate and limitations of therapeutic targets become major obstacles to its clinical application. Recent studies have shown that CD24 is involved in an important process of tumor immune regulation in breast cancer and is a promising target for immunotherapy.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In this study, singleR was used to annotate each cell subpopulation after t-distributed stochastic neighbor embedding (t-SNE) methods. Pseudo-time trace analysis and cell communication were analyzed by Monocle2 package and CellChat, respectively. A prognostic model based on CD24-related genes was constructed using several machine learning methods. Multiple quantitative immunofluorescence (MQIF) was used to evaluate the spatial relationship between CD24⁺PANCK⁺cells and exhausted CD8⁺T cells.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Based on the scRNA-seq analysis, 1488 CD24-related differential genes were identified, and a risk model consisting of 15 prognostic characteristic genes was constructed by combining the bulk RNA-seq data. Patients were divided into high- and low-risk groups based on the median risk score. Immune landscape analysis showed that the low-risk group showed higher infiltration of immune-promoting cells and stronger immune reactivity. The results of cell communication demonstrated a strong interaction between CD24⁺epithelial cells and CD8⁺T cells. Subsequent MQIF demonstrated a strong interaction between CD24⁺PANCK⁺ and exhausted CD8⁺T cells with FOXP3⁺ in breast cancer. Additionally, CD24⁺PANCK⁺ and CD8⁺FOXP3⁺T cells were positively associated with lower survival rates.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This study highlights the importance of CD24⁺breast cancer cells in clinical prognosis and immunosuppressive microenvironment, which may provide a new direction for improving patient outcomes.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of liver macrophages, gut microbiota, and bile acid metabolism on the differences in iHFC diet-induced MASH progression between TSNO and TSOD mice","authors":"Naoya Igarashi, Kaichi Kasai, Yuki Tada, Koudai Kani, Miyuna Kato, Shun Takano, Kana Goto, Yudai Matsuura, Mayuko Ichimura-Shimizu, Shiro Watanabe, Koichi Tsuneyama, Yukihiro Furusawa, Yoshinori Nagai","doi":"10.1007/s00011-024-01884-7","DOIUrl":"https://doi.org/10.1007/s00011-024-01884-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Tsumura-Suzuki non-obese (TSNO) mice exhibit a severe form of metabolic dysfunction-associated steatohepatitis (MASH) with advanced liver fibrosis upon feeding a high-fat/cholesterol/cholate-based (iHFC) diet. Another ddY strain, Tsumura-Suzuki diabetes obese (TSOD) mice, are impaired in the progression of iHFC diet-induced MASH.</p><h3 data-test=\"abstract-sub-heading\">Aim</h3><p>To elucidate the underlying mechanisms contributing to the differences in MASH progression between TSNO and TSOD mice.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We analyzed differences in the immune system, gut microbiota, and bile acid metabolism in TSNO and TSOD mice fed with a normal diet (ND) or an iHFC diet.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>TSOD mice had more anti-inflammatory macrophages in the liver than TSNO mice under ND feeding, and were impaired in the iHFC diet-induced accumulation of fibrosis-associated macrophages and formation of histological hepatic crown-like structures in the liver. The gut microbiota of TSOD mice also exhibited a distinct community composition with lower diversity and higher abundance of <i>Akkermansia muciniphila</i> compared with that in TSNO mice. Finally, TSOD mice had lower levels of bile acids linked to intestinal barrier disruption under iHFC feeding.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The dynamics of liver macrophage subsets, and the compositions of the gut microbiota and bile acids at steady state and post-onset of MASH, had major impacts on MASH development.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140585062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute lung injury: a view from the perspective of necroptosis","authors":"Jinyan Dong, Weihong Liu, Wenli Liu, Yuqi Wen, Qingkuo Liu, Hongtao Wang, Guohan Xiang, Yang Liu, Hao Hao","doi":"10.1007/s00011-024-01879-4","DOIUrl":"https://doi.org/10.1007/s00011-024-01879-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>ALI/ARDS is a syndrome of acute onset characterized by progressive hypoxemia and noncardiogenic pulmonary edema as the primary clinical manifestations. Necroptosis is a form of programmed cell necrosis that is precisely regulated by molecular signals. This process is characterized by organelle swelling and membrane rupture, is highly immunogenic, involves extensive crosstalk with various cellular stress mechanisms, and is significantly implicated in the onset and progression of ALI/ARDS.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The current body of literature on necroptosis and ALI/ARDS was thoroughly reviewed. Initially, an overview of the molecular mechanism of necroptosis was provided, followed by an examination of its interactions with apoptosis, pyroptosis, autophagy, ferroptosis, PANOptosis, and NETosis. Subsequently, the involvement of necroptosis in various stages of ALI/ARDS progression was delineated. Lastly, drugs targeting necroptosis, biomarkers, and current obstacles were presented.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Necroptosis plays an important role in the progression of ALI/ARDS. However, since ALI/ARDS is a clinical syndrome caused by a variety of mechanisms, we emphasize that while focusing on necroptosis, it may be more beneficial to treat ALI/ARDS by collaborating with other mechanisms.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tryptophan catabolism via the kynurenine pathway regulates infection and inflammation: from mechanisms to biomarkers and therapies","authors":"Jingpu Zhang, Yanlei Liu, Xiao Zhi, Li Xu, Jie Tao, Daxiang Cui, Tie Fu Liu","doi":"10.1007/s00011-024-01878-5","DOIUrl":"https://doi.org/10.1007/s00011-024-01878-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p><span>l</span>-Tryptophan (<span>l</span>-Trp), an essential amino acid, is the only amino acid whose level is regulated specifically by immune signals. Most proportions of Trp are catabolized via the kynurenine (Kyn) pathway (KP) which has evolved to align the food availability and environmental stimulation with the host pathophysiology and behavior. Especially, the KP plays an indispensable role in balancing the immune activation and tolerance in response to pathogens.</p><h3 data-test=\"abstract-sub-heading\">Scope of review</h3><p>In this review, we elucidate the underlying immunological regulatory network of Trp and its KP-dependent catabolites in the pathophysiological conditions by participating in multiple signaling pathways. Furthermore, the KP-based regulatory roles, biomarkers, and therapeutic strategies in pathologically immune disorders are summarized covering from acute to chronic infection and inflammation.</p><h3 data-test=\"abstract-sub-heading\">Major conclusions</h3><p>The immunosuppressive effects dominate the functions of KP induced-Trp depletion and KP-produced metabolites during infection and inflammation. However, the extending minor branches from the KP are not confined to the immune tolerance, instead they go forward to various functions according to the specific condition. Nevertheless, persistent efforts should be made before the clinical use of KP-based strategies to monitor and cure infectious and inflammatory diseases.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage-enriched novel functional long noncoding RNAs LRRC75A-AS1 and GAPLINC regulate polarization and innate immune responses","authors":"Araceli Valverde, Raza Ali Naqvi, Afsar R. Naqvi","doi":"10.1007/s00011-024-01865-w","DOIUrl":"https://doi.org/10.1007/s00011-024-01865-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Macrophages (Mφs) are functionally dynamic immune cells that bridge innate and adaptive immune responses; however, the underlying epigenetic mechanisms that control Mφ plasticity and innate immune functions are not well elucidated.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>To identify novel functions of macrophage-enriched lncRNAs in regulating polarization and innate immune responses.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Total RNA isolated from differentiating monocyte-derived M1 and M2 Mφs was profiled for lncRNAs expression using RNAseq. Impact of LRRC75A-AS1, GAPLINC and AL139099.5 knockdown was examined on macrophage differentiation, polarization markers, phagocytosis, and antigen processing by flow cytometry and florescence microscopy. Cytokine profiles were examined by multiplex bead array and cytoskeletal signaling pathway genes were quantified by PCR-based array. Gingival biopsies were collected from periodontally healthy and diseased subjects to examine lncRNAs, M1/M2 marker expression.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Transcriptome profiling of M1 and M2 Mφs identified thousands of differentially expressed known and novel lncRNAs. We characterized three Mφ-enriched lncRNAs LRRC75A-AS1, GAPLINC and AL139099.5 in polarization and innate immunity. Knockdown of LRRC75A-AS1 and GAPLINC downregulated the Mφ differentiation markers and skewed Mφ polarization by decreasing M1 markers without a significant impact on M2 markers. LRRC75A-AS1 and GAPLINC knockdown also attenuated bacterial phagocytosis, antigen processing and inflammatory cytokine secretion in Mφs, supporting their functional role in potentiating innate immune functions. Mechanistically, LRRC75A-AS1 and GAPLINC knockdown impaired Mφ migration by downregulating the expression of multiple cytoskeletal signaling pathways suggesting their critical role in regulating Mφ migration. Finally, we showed that LRRC75A-AS1 and GAPLINC were upregulated in periodontitis and their expression correlates with higher M1 markers suggesting their role in macrophage polarization in vivo.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our results show that polarized Mφs acquire a unique lncRNA repertoire and identified many previously unknown lncRNA sequences. LRRC75A-AS1 and GAPLINC, which are induced in periodontitis, regulate Mφ polarization and innate immune functions supporting their critical role in inflammation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic analysis reveals molecular characterization and immune landscape of PANoptosis-related genes in atherosclerosis","authors":"Zhipeng Zheng, Kaiyuan Li, Zhiyuan Yang, Xiaowen Wang, Cheng Shen, Yubin Zhang, Huimin Lu, Zhifeng Yin, Min Sha, Jun Ye, Li Zhu","doi":"10.1007/s00011-024-01877-6","DOIUrl":"https://doi.org/10.1007/s00011-024-01877-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Atherosclerosis is a chronic inflammatory disease characterized by abnormal lipid deposition in the arteries. Programmed cell death is involved in the inflammatory response of atherosclerosis, but PANoptosis, as a new form of programmed cell death, is still unclear in atherosclerosis. This study explored the key PANoptosis-related genes involved in atherosclerosis and their potential mechanisms through bioinformatics analysis.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We evaluated differentially expressed genes (DEGs) and immune infiltration landscape in atherosclerosis using microarray datasets and bioinformatics analysis. By intersecting PANoptosis-related genes from the GeneCards database with DEGs, we obtained a set of PANoptosis-related genes in atherosclerosis (PANoDEGs). Functional enrichment analysis of PANoDEGs was performed and protein–protein interaction (PPI) network of PANoDEGs was established. The machine learning algorithms were used to identify the key PANoDEGs closely linked to atherosclerosis. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic potency of key PANoDEGs. CIBERSORT was used to analyze the immune infiltration patterns in atherosclerosis, and the Spearman method was used to study the relationship between key PANoDEGs and immune infiltration abundance. The single gene enrichment analysis of key PANoDEGs was investigated by GSEA. The transcription factors and target miRNAs of key PANoDEGs were predicted by Cytoscape and online database, respectively. The expression of key PANoDEGs was validated through animal and cell experiments.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>PANoDEGs in atherosclerosis were significantly enriched in apoptotic process, pyroptosis, necroptosis, cytosolic DNA-sensing pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis. Four key PANoDEGs (ZBP1, SNHG6, DNM1L, and AIM2) were found to be closely related to atherosclerosis. The ROC curve analysis demonstrated that the key PANoDEGs had a strong diagnostic potential in distinguishing atherosclerotic samples from control samples. Immune cell infiltration analysis revealed that the proportion of initial B cells, plasma cells, CD4 memory resting T cells, and M1 macrophages was significantly higher in atherosclerotic tissues compared to normal tissues. Spearman analysis showed that key PANoDEGs showed strong correlations with immune cells such as T cells, macrophages, plasma cells, and mast cells. The regulatory networks of the four key PANoDEGs were established. The expression of key PANoDEGs was verified in further cell and animal experiments.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This study evaluated the expression changes of PANoptosis-related genes in atherosclerosis, providing a reference direction for the study of PANoptosis in atherosclerosis and offering potential new avenues for further under","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}