Journal of Inflammation-London最新文献

{"title":"The injury effect of osteopontin in sepsis-associated lung injury.","authors":"Qian Wang, Zhicai Yu, Zhixin Song, Xue Lu, Zhu Li, Dandan Pi, Jing Li, Feng Xu","doi":"10.1186/s12950-025-00430-4","DOIUrl":"10.1186/s12950-025-00430-4","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a severe condition causing organ failure due to an abnormal immune reaction to infection, characterized by ongoing excessive inflammation and immune system issues. Osteopontin (OPN) is secreted by various cells and plays a crucial role in inflammatory responses and immune regulation. Nonetheless, the precise function of OPN in sepsis remains to be elucidated.</p><p><strong>Methods: </strong>In the present study, we evaluated the levels of OPN in paediatric patients with sepsis and healthy individuals. We examined the impact of OPN on survival rates, systemic inflammation, and lung injury within an experimental sepsis model using cecal ligation and puncture (CLP). Furthermore, the pro-inflammatory effects and potential mechanisms of OPN in sepsis were investigated through Mouse Hemophagocytic Synuclein (MH-S) cells.</p><p><strong>Results: </strong>The OPN level was found to be elevated in patients with sepsis (368.5 ± 249.4 ng/ml) compared to children with infections (73.78 ± 40.46 ng/ml) (p < 0.0001) and healthy individuals (44.03 ± 20.76 ng/ml) (p < 0.0001). The serum concentration of OPN was elevated in pediatric patients with septic shock compared to those with sepsis (504 ± 266.3 ng/ml vs. 238.6 ± 143.8 ng/ml, p < 0.001). Intravenous administration of OPN inhibitor into the tail vein decreased the mortality rate (HR = 0.2695, p = 0.0015), suppressed systemic inflammatory responses and mitigated lung tissue damage. The concentration of tumour necrosis factor (TNF)-α, IL-6 and IL-1β in serum of CLP mice treated with OPN inhibitor decreased compared with CLP mice. Within the sepsis mouse model, there was a marked increase in OPN expression in the lung's tissues compared to the sham group mice. This surge was accompanied by a significant accumulation of alveolar macrophages and an upregulation of inflammasome expression. Mechanistic investigations in MH-s cells revealed that OPN-siRNA suppressed the LPS-induced macrophage inflammatory response by inhibiting caspase1-dependent classical pyroptosis signaling pathway. However, recombinant OPN was supplemented after OPN silencing, the protective effects in MH-s cells treated with LPS were reversed.</p><p><strong>Conclusion: </strong>This study reveals that OPN has an adverse impact on the host's immune response to sepsis. Suppressing OPN expression holds potential therapeutic value for the treatment of sepsis.</p><p><strong>Trial registration: </strong>Study on the diagnostic value of osteopontin in children with sepsis. MR5024001771. Registered 22 January 2024. https//www.medicalresearch.org.cn.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"4"},"PeriodicalIF":4.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPV4 modulates inflammatory responses and apoptosis in enteric glial cells triggered by Clostridioides difficile toxins A and B.","authors":"Dvison de Melo Pacífico, Deiziane Viana da Silva Costa, Maria Lucianny Lima Barbosa, Conceição Silva Martins Rebouças, Simone de Goes Simonato, Cirle Alcantara Warren, Maria Luana Gaudencio Dos Santos Morais, Renata Ferreira de Carvalho Leitao, Gerly Anne de Castro Brito","doi":"10.1186/s12950-024-00425-7","DOIUrl":"10.1186/s12950-024-00425-7","url":null,"abstract":"<p><p>Clostridioides difficile, a spore-forming anaerobic bacterium, is the primary cause of hospital antibiotic-associated diarrhea. Key virulence factors, toxins A (TcdA) and B (TcdB), significantly contribute to C. difficile infection (CDI). Yet, the specific impact of these toxins, particularly on enteric glial cells (EGCs), still needs to be fully understood. This study examines the role of the transient receptor potential vanilloid 4 (TRPV4), a calcium-permeable channel, in the inflammatory response and apoptosis of EGCs induced by TcdA and TcdB and evaluates TRPV4 expression in the cecum and colon of infected mice. EGCs were treated with TcdA (50ng/mL) or TcdB (1ng/mL) for 18 h, with or without the TRPV4 antagonist RN-1734 (100 µM), to assess TRPV4 gene and protein levels, inflammatory markers, and cell death. C. difficile infected mice were euthanized on day 3 post-infection for TRPV4 expression in the cecum and colon. Findings reveal that EGCs naturally express TRPV4, increasing its expression by TcdA and TcdB exposure. CDI significantly upregulates TRPV4 in the cecum and colon's submucosal and myenteric plexus regions. TRPV4 mediates TNF-α release in EGCs and is partially involved in the increase in IL-6 gene expression triggered by these toxins. Our results highlight TRPV4's role in triggering EGC apoptosis via caspase 3 activation and inhibiting the reduction of Bcl-2, an anti-apoptotic protein in EGCs caused by C. difficile toxins. These results highlight TRPV4's significant role in CDI pathogenesis and its potential as a therapeutic target to counteract the detrimental effects of C. difficile toxins on enteric glia.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"3"},"PeriodicalIF":4.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Progress of CCL20-CCR6 in the airways: a promising new therapeutic target.","authors":"Ya -Jing Li, Wan-Li Geng, Chen-Chen Li, Jia-Hao Wu, Fei Gao, Yong Wang","doi":"10.1186/s12950-025-00428-y","DOIUrl":"10.1186/s12950-025-00428-y","url":null,"abstract":"","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"2"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Downregulation of miR-223 promotes HMGB2 expression and induces oxidative stress to activate JNK and promote autophagy in an in vitro model of acute lung injury.","authors":"Hao-Yu Tan, Bei Qing, Xian-Mei Luo, Heng-Xing Liang","doi":"10.1186/s12950-024-00424-8","DOIUrl":"https://doi.org/10.1186/s12950-024-00424-8","url":null,"abstract":"","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"1"},"PeriodicalIF":4.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress of CCL20-CCR6 in the airways: a promising new therapeutic target.","authors":"Ya -Jing Li, Wan-Li Geng, Chen-Chen Li, Jia-Hao Wu, Fei Gao, Yong Wang","doi":"10.1186/s12950-024-00427-5","DOIUrl":"10.1186/s12950-024-00427-5","url":null,"abstract":"<p><p>The chemokine CCL20, a small cytokine that belongs to the C-C chemokine family, interacts with its homologous receptor CCR6, which is expressed on wide range of cell types. According to current research, the CCL20-CCR6 has been established as acritical player in a diverse range of inflammatory, oncogenic, and autoimmune diseases. Within the respiratory system, CCL20-CCR6 demonstrates heightened expression in conditions such as allergic asthma, chronic airway inflammation, non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), and other respiratory diseases, which is conducive to the inflammatory mediators recruitment and tumor microenvironment remodeling. Numerous studies have demonstrated that therapeutic interventions targeting CCL20 and CCR6, including antibodies and antagonists, have the potential to mitigate disease progression. Despite the promising research prospects surrounding the CCL20-CCR6 chemokine axis, the precise mechanisms underlying its action in respiratory diseases remain largely elusive. In this review, we delve into the potential roles of the CCL20-CCR6 axis within the respiratory system by synthesizing and analyzing current research findings. Our objective is to provide a comprehensive understanding of the CCL20-CCR6 axis and its implications for respiratory health and disease. And we aspire to propel research endeavors in this domain and furnish valuable insights for the development of future therapeutic strategies.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"54"},"PeriodicalIF":4.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basement membranes' role in immune cell recruitment to the central nervous system.","authors":"Shaun A Wright, Rachel Lennon, Andrew D Greenhalgh","doi":"10.1186/s12950-024-00426-6","DOIUrl":"10.1186/s12950-024-00426-6","url":null,"abstract":"<p><p>Basement membranes form part of the extracellular matrix (ECM), which is the structural basis for all tissue. Basement membranes are cell-adherent sheets found between cells and vascular endothelia, including those of the central nervous system (CNS). There is exceptional regional specialisation of these structures, both in tissue organisation and regulation of tissue-specific cellular processes. Due to their location, basement membranes perform a key role in immune cell trafficking and therefore are important in inflammatory processes causing or resulting from CNS disease and injury. This review will describe basement membranes in detail, with special focus on the brain. We will cover how genetic changes drive brain pathology, describe basement membranes' role in immune cell recruitment and how they respond to various brain diseases. Understanding how basement membranes form the junction between the immune and central nervous systems will be a major advance in understanding brain disease.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"53"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of statins on arterial wall inflammation as assessed by 18F-FDG PET CT: an updated systematic review and meta-analysis.","authors":"Tannaz Jamialahmadi, Željko Reiner, Luis E Simental-Mendia, Wael Almahmeed, Sercan Karav, Ali H Eid, Francesco Giammarile, Amirhossein Sahebkar","doi":"10.1186/s12950-024-00421-x","DOIUrl":"10.1186/s12950-024-00421-x","url":null,"abstract":"<p><strong>Background: </strong>Pathogenesis of atherosclerosis is largely mediated by inflammatory process. Statins are lipid-lowering drugs which also have anti-inflammatory effects. 18 fluorine radiolabeled fluorodeoxyglucose (18 F-FDG) positron emission tomography-computed tomography (PET-CT) is considered to be a good indicator of arterial wall inflammation. Therefore, in this meta-analysis the role of statins on inflammatory process in the artery wall was evaluated using this method since its actual validity for this purpose is not yet well established.</p><p><strong>Methods: </strong>PubMed, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases were searched using MESH terms and keywords. Funnel plot, Begg's rank correlation, and Egger's weighted regression tests evaluated publication bias in the meta-analysis. In cases where funnel plot asymmetry was observed, the \"trim and fill\" method was used to check the input of potentially missing studies.</p><p><strong>Results: </strong>Findings of 10 clinical trials involving 373 subjects showed a remarkable reduction of arterial wall 18 F-FDG uptake according to target-to-background ratio (TBR) index after treatment with statins. Subgroup analysis showed a significant decrease in TBR with high-intensity and non-significant reduction of TBR with low-to-moderate-intensity statin therapy.</p><p><strong>Conclusion: </strong>Treatment with statins suppressed arterial wall inflammation as shown by using 18 F-FDG PET-CT.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"52"},"PeriodicalIF":4.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory effects of statins on CCL2/CCR2 axis in cardiovascular diseases: new insight into pleiotropic effects of statins.","authors":"Hanieh Gholamalizadeh, Behzad Ensan, Sercan Karav, Tannaz Jamialahmadi, Amirhossein Sahebkar","doi":"10.1186/s12950-024-00420-y","DOIUrl":"10.1186/s12950-024-00420-y","url":null,"abstract":"<p><strong>Background: </strong>HMG-CoA reductase inhibitors are well-known medications in the treatment of cardiovascular disorders due to their pleiotropic and lipid-lowering properties. Herein, we reviewed the effects of statins on the CCL2/CCR2 axis.</p><p><strong>Method: </strong>Scopus and Pubmed databases were systematically searched using the following keywords:\" Hydroxymethylglutaryl CoA Reductase Inhibitors\",\" HMG-CoA Reductase Inhibitors\",\" Statins\", \"CCL2, Chemokine\", \"Monocyte Chemoattractant Protein-1\" and \"Chemokine (C-C Motif) Ligand 2\". Evidence investigating the role of statin on MCP-1 in CVD was identified and bibliographies were completely evaluated to gather further related studies.</p><p><strong>Results: </strong>The anti-inflammatory effects of statins on the CCL2/CCR2 pathway have been widely investigated. Despite inconclusive results, a great body of research supports the regulatory roles of statins on this pathway due to their pleiotropic effects. By disrupting the CCL2/CCR2 axis, statins attenuate the infiltration of monocytes and macrophages into the zone of inflammation and hence down-regulate the inflammatory cascades in various CVDs including atherosclerosis, cardiac remodeling, and stroke, among others.</p><p><strong>Conclusion: </strong>CCL2 plays a major role in the pathogenesis of cardiovascular disorders. Down-regulation of CCL2 is proposed as one of the pleiotropic properties of statins. However, more investigations are required to elucidate which statin in what dose exerts a more potent effect on CCL2/CCR2 pathway.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"51"},"PeriodicalIF":4.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolution of acute inflammation induced by monosodium urate crystals (MSU) through neutrophil extracellular trap-MSU aggregate-mediated negative signaling.","authors":"Cheng-Hsun Lu, Chieh-Yu Shen, Ko-Jen Li, Cheng-Han Wu, Yu-Hsuan Chen, Yu-Min Kuo, Song-Chou Hsieh, Chia-Li Yu","doi":"10.1186/s12950-024-00423-9","DOIUrl":"10.1186/s12950-024-00423-9","url":null,"abstract":"<p><strong>Background: </strong>Polymorphonuclear neutrophils (PMN) activation by monosodium urate crystals (MSU) is crucial to acute gouty arthritis and subsequent spontaneous remission within 7-10 days. Activated PMNs release neutrophil extracellular traps (NETs) that entrap MSU crystals, forming NET-MSU aggregates. Whether NET-MSU aggregates contribute to the resolution of acute inflammation remains to be elucidated. This study uses a cell-based approach to unveil their molecular bases.</p><p><strong>Methods: </strong>All-trans retinoic acid-differentiated HL-60 cells (dHL-60) served as surrogate PMNs. NET release from MSU-activated dHL-60 was confirmed by detecting DNA, neutrophil elastase, and citrullinated histone 3, forming large NET-MSU aggregates. NET area was measured with Fiji software after SYTOX Green staining. Released pro-inflammatory cytokines IL-8 and TNF-α, and the anti-inflammatory cytokine IL-1RA in culture supernatants were quantified to calculate the estimate inflammation score (EIS). Cellular redox state was determined by a FRET-based sensor. Expression of intracellular positive (ERK1/2) and negative (SHP-1 and SHIP-1) cytokine signaling regulators was detected by western blot. qPCR detected mRNA expressions of CISH and SOCS1-SOCS7. Flow cytometry measured neutrophil N1 (CD54) and N2 (CD182) surface markers after staining with fluorescent-conjugated antibodies.</p><p><strong>Results: </strong>Incubating dHL-60 with MSU for 4 h maximized NET-MSU aggregate formation and acute inflammation with an EIS of 11.6. Prolonging the incubation of dHL-60 + MSU to 22 h gradually raised the EIS to 19.40 without increasing NET area, due to reduced cellular redox capacity. Adding both new dHL-60 and new MSU crystals to the culture, mimicking the clinical scenario, increased NET area but conversely suppressed EIS to 1.53, indicating acute inflammation resolution. The resolution of acute inflammation following prolonged incubation was attributed to decreases in P-ERK and increases in P-SHP-1, SOCS2, SOCS3, and CISH gene expressions, which may suppress pro-inflammatory and enhance anti-inflammatory cytokine production. Moreover, the large NET-MSU aggregates facilitated N1 to N2 polarization, crucial for accelerating inflammation resolution.</p><p><strong>Conclusion: </strong>We explored the potential molecular basis for the spontaneous resolution of MSU induced acute inflammation using a cell-based model in that huge NET-MSU aggregates frustrate the transformation of newly entering PMNs to the N2 phenotype, enhancing the production of the anti-inflammatory cytokine IL-1RA.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"50"},"PeriodicalIF":4.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage involvement in idiopathic inflammatory myopathy: pathogenic mechanisms and therapeutic prospects.","authors":"Ziqi Li, Huan Liu, Qibing Xie, Geng Yin","doi":"10.1186/s12950-024-00422-w","DOIUrl":"10.1186/s12950-024-00422-w","url":null,"abstract":"<p><p>Idiopathic inflammatory myopathies are a group of systemic autoimmune diseases characterized by chronic muscle inflammation and diverse clinical manifestations. Macrophages, pivotal components of innate immunity, are implicated in immune responses, inflammation resolution, and tissue repair. Distinct macrophage polarization states play vital roles in disease progression and resolution. Mechanistically, activated macrophages release proinflammatory cytokines, chemokines, and reactive oxygen species, perpetuating immune responses and tissue damage. Dysregulated macrophage polarization contributes to sustained inflammation. Here, we reviewed the intricate contributions of macrophages to IIM pathogenesis and explored novel therapeutic avenues. We discussed emerging strategies targeting macrophages, including receptor-based interventions and macrophage polarization modulation, for IIM treatment. This review underscores the multifaceted involvement of macrophages in IIM pathogenesis and offers insights into potential therapeutic approaches targeting these immune cells for disease management.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"48"},"PeriodicalIF":4.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}