Inflammation Research最新文献

{"title":"Silencing aquaporin 1 inhibits autophagy to exert anti-rheumatoid arthritis effects in TNF-α-induced fibroblast-like synoviocytes and adjuvant-induced arthritis rats","authors":"Man-Yu Zhang, Meng-Qing Wang, Yan Huang, Sheng-Long Gu, Meng-Yuan Zhou, Ze-Shan Xu, Ling-Ling Li, Min Lv, Li Cai, Rong Li","doi":"10.1007/s00011-024-01966-6","DOIUrl":"10.1007/s00011-024-01966-6","url":null,"abstract":"<p><strong>Objective: </strong>Fibroblast-like synoviocytes (FLS) are key players in rheumatoid arthritis (RA) by resisting apoptosis via increased autophagy. Elevated synovial aquaporin 1 (AQP1) affects RA FLS behaviors, but its relationship with FLS autophagy is unclear. We aim to clarify that silencing AQP1 inhibits autophagy to exert its anti-RA effects.</p><p><strong>Methods: </strong>We studied the effects and mechanisms of AQP1 silencing on autophagy in TNF-α-induced RA FLS and examined the crucial role of autophagy inhibition in its impacts on RA FLS pathogenic behaviors. We explored whether silencing synovial AQP1 relieved rat adjuvant-induced arthritis (AIA) by reducing synovial autophagy.</p><p><strong>Results: </strong>TNF-α stimulation increased AQP1 expression and autophagy levels in RA FLS, with a positive correlation between them. AQP1 silencing inhibited autophagy in TNF-α-stimulated RA FLS, along with suppressing proliferation, promoting apoptosis, and mitigating inflammation. Notably, the inhibitory effects of AQP1 silencing on RA FLS pathogenic behaviors were cancelled by autophagy activation with rapamycin (Rapa) but enhanced by autophagy inhibition using 3-Methyladenine. Mechanistically, silencing AQP1 enhanced the binding of Bcl-2 to Beclin1 by decreasing Beclin1-K63 ubiquitination, thus inhibiting RA FLS autophagy. In vivo, silencing synovial AQP1 relieved the severity and development of rat AIA, alongside reducing Ki67 expression, promoting apoptosis, and decreasing autophagy within AIA rat synovium. Expectedly, the Rapa co-administration nullified the anti-AIA effects of silencing synovial AQP1.</p><p><strong>Conclusion: </strong>These findings reveal that silencing AQP1 inhibits RA FLS pathogenic behaviors and attenuates rat AIA through autophagy inhibition. This study may help clarify the pathogenic role of AQP1 in enhancing autophagy during RA development.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"12"},"PeriodicalIF":4.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948003","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":"Mitochondrial damage causes inflammation via cGAS-STING signaling in ketamine-induced cystitis.","authors":"Jinji Chen, Shengsheng Liang, Cheng Li, Bowen Li, Mingdong He, Kezhen Li, Weijin Fu, Shenghua Li, Hua Mi","doi":"10.1007/s00011-024-01973-7","DOIUrl":"https://doi.org/10.1007/s00011-024-01973-7","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial dysfunction and damage can result in the release of mitochondrial DNA (mtDNA) into the cytoplasm, which subsequently activates the cGAS-STING pathway, promoting the onset of inflammatory diseases. Various factors, such as oxidative stress, viral infection, and drug toxicity, have been identified as inducers of mitochondrial damage. This study aims to investigate the role of mtDNA as a critical inflammatory mediator in the pathogenesis of ketamine (KET)-induced cystitis (KC) through the cGAS-STING pathway.</p><p><strong>Methods: </strong>To investigate the role of the cGAS-STING pathway in KET-induced cystitis, we assessed the expression of cGAS and STING in rats with KET cystitis. Additionally, we evaluated STING expression in conditionally deficient Simian Virus-transformed Human Uroepithelial Cell Line 1 (SV-HUC-1) cells in vitro. Morphological changes in mitochondria were examined using transmission electron microscopy. We measured intracellular reactive oxygen species (ROS) production through flow cytometry and immunofluorescence techniques. Furthermore, alterations in associated inflammatory factors and cytokines were quantified using real-time quantitative PCR with fluorescence detection.</p><p><strong>Results: </strong>We observed up-regulation of cGAS and STING expressions in the bladder tissue of rats in the KET group, stimulation with KET also led to increased cGAS and STING levels in SV-HUC-1 cells. Notably, the knockdown of STING inhibited the nuclear translocation of NF-κB p65 and IRF3, resulting in a decrease in the expression of inflammatory cytokines, including IL-6, IL-8, and CXCL10. Additionally, KET induced damage to the mitochondria of SV-HUC-1 cells, facilitating the release of mtDNA into the cytoplasm. This significant depletion of mtDNA inhibited the activation of cGAS-STING pathway, subsequently affecting the expression of NF-κB p65 and IRF3. Importantly, the reintroduction of mtDNA after STING knockdown partially restored the inflammatory response.</p><p><strong>Conclusion: </strong>Our findings confirmed the activation of the cGAS-STING pathway in KC rats and revealed mitochondrial damage in vitro. These results highlight the involvement of the cGAS-STING pathway in the pathogenesis of KC, suggesting its potential as a therapeutic target for intervention.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"6"},"PeriodicalIF":4.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055933","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":"Mechanistic and therapeutic insights into the function of N6-methyladenosine in arthritic diseases.","authors":"Xinyue Zhou, Yajie Wu, Yingqiu Song, Bing Wang, Yikang Cai, Chenggui Miao","doi":"10.1007/s00011-024-01969-3","DOIUrl":"https://doi.org/10.1007/s00011-024-01969-3","url":null,"abstract":"<p><strong>Objective: </strong>Arthritis is a class of diseases, characterized by joint and surrounding inflammation, accompanied by joint swelling, pain, dysfunction. According to different factors, arthritis can be divided into osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and so on. N6-methyladenosine (m6A) is the most common internal modification of eukaryotic mRNA and is involved in splicing, stabilization, output and degradation of RNA metabolism. This review systematically summarized current insights into the mechanism of m6A in arthritis.</p><p><strong>Methods: </strong>The studies related to the involvement of m6A in the pathogenesis of arthritis reported in PubMed, Google scholar, and other open source literatures were investigated to evaluate the important roles of m6A in arhtritis, and the clinical relevances.</p><p><strong>Results and conclusions: </strong>M6A methylation regulators play the roles of writers, erasers, and readers, are crucial for regulating gene expression, and play important roles in many biological processes such as virus replication and cell differentiation. In addition, more and more studies have shown that m6A is closely related to the development of arthritis. As a new therapeutic target for arthritis, m6A has a wide influence on the pathological mechanism of arthritis. However, further research is needed to determine how m6A affects arthritis pathology and its use in target therapy and diagnosis.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"7"},"PeriodicalIF":4.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947998","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":"Targeting mitochondrial function as a potential therapeutic approach for allergic asthma.","authors":"Daichi Chen, Wanhua Wu, Jianing Li, Xueqin Huang, Su Chen, TingTing Zheng, Gonghua Huang, Suidong Ouyang","doi":"10.1007/s00011-024-01972-8","DOIUrl":"https://doi.org/10.1007/s00011-024-01972-8","url":null,"abstract":"<p><p>Allergic asthma is a chronic complex airway disease characterized by airway hyperresponsiveness, eosinophilic inflammation, excessive mucus secretion, and airway remodeling, with increasing mortality and incidence globally. The pathogenesis of allergic asthma is influenced by various factors including genetics, environment, and immune responses, making it complex and diverse. Recent studies have found that various cellular functions of mitochondria such as calcium regulation, adenosine triphosphate production, changes in redox potential, and free radical scavenging, are involved in regulating the pathogenesis of asthma. This review explores the involvement of mitochondrial functional changes in the pathogenesis of asthma, and investigate the potential of targeting cellular mitochondria as a therapeutic approach for asthma. Those insights can provide a novel theoretical foundations and treatment strategies for understanding and preventing asthma.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"1"},"PeriodicalIF":4.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948006","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":"Causal genes identification of giant cell arteritis in CD4+ Memory t cells: an integration of multi-omics and expression quantitative trait locus analysis.","authors":"Qiyi Yu, Yifan Wu, Xianda Ma, Yidong Zhang","doi":"10.1007/s00011-024-01965-7","DOIUrl":"https://doi.org/10.1007/s00011-024-01965-7","url":null,"abstract":"<p><strong>Background: </strong>Giant cell arteritis (GCA) is a prevalent artery and is strongly correlated with age. The role of CD4+ Memory T cells in giant cell arteritis has not been elucidated.</p><p><strong>Method: </strong>Through single-cell analysis, we focused on the CD4+ Memory T cells in giant cell arteritis. eQTL analysis and mendelian randomization analysis identified the significant genes which have a causal effect on giant cell arteritis risk. CD4+ Memory T cells were subsequently divided into gene-positive and gene-negative groups, then further single-cell analysis was conducted. Mendelian randomization of plasma proteins, blood-urine biomarkers and metabolites were also performed. Eventually, the PMA induced Jurkat cell lines were used for biological experiments to explore the specific functions of significant causal genes in CD4+ Memory T cells.</p><p><strong>Results: </strong>Similarity of CD4+ Memory T cells in GCA and old samples were explored. DDIT4 and ARHGAP15 were identified as significant risk genes via mendelian randomization. The CD4+ Memory T cells were then divided into DDIT4 ± or ARHGAP15 ± groups, and further single-cell analysis indicated the differences in aspects involving intercellular communication, functional pathways, protein activity, metabolism and drug sensitivity between positive and negative groups. In vitro experiments, including overexpression and knockdown, demonstrated that DDIT4 leading to a chronic, low-intensity inflammatory state in CD4+ Memory T cells, eventually promoting the development of GCA.</p><p><strong>Conclusion: </strong>DDIT4 and ARHGAP15 have significant causal effects on giant cell arteritis risk. Specifically, DDIT4 exhibit pro-inflammatory effects on GCA via promotes chronic, low-intensity inflammatory in CD4+ Memory T cell.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"3"},"PeriodicalIF":4.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946867","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":"A universal gene expression signature-based strategy for the high-throughput discovery of anti-inflammatory drugs.","authors":"Juan Feng, Honglei Dang, Xiaoling Zhang, Wenting Huang, Chengmei Ma, Aixiang Zhang, Mimi Hao, Lan Xie","doi":"10.1007/s00011-024-01968-4","DOIUrl":"https://doi.org/10.1007/s00011-024-01968-4","url":null,"abstract":"<p><strong>Background: </strong>Traditional Chinese medicine (TCM) is a valuable resource for drug discovery and has demonstrated excellent efficacy in treating inflammatory diseases. This study aimed to develop a universal gene signature-based strategy for high-throughput discovery of anti-inflammatory drugs, especially Traditional Chinese medicine (TCM).</p><p><strong>Methods: </strong>The disease gene signature of liposaccharide-stimulated THP-1 cells and drug gene signatures of 655 drug candidates were established via sequencing. Anti-inflammatory drugs were screened based on similarities between drug gene signatures and the reversed disease gene signature.</p><p><strong>Results: </strong>Through screening, 83 potential anti-inflammatory drugs were identified. The efficacy of the TCM formula Biyun Powder, along with individual TCMs, Centipedea Herba, Kaempferiae Rhizoma, and Schizonepetae Spica Carbonisata, was verified in vitro or in vivo. Mechanistically, they exerted anti-inflammatory effects by inhibiting the nuclear factor-kappa B pathway. Kaempferol and luteolin were identified as bioactive IκB kinase-β inhibitors in Kaempferiae Rhizoma and Schizonepetae Spica Carbonisata, respectively.</p><p><strong>Conclusion: </strong>We developed a universal gene signature-based approach for the high-throughput discovery of anti-inflammatory drugs that is applicable to compounds and to TCM herbs/formulae and established a workflow (screening, validation of efficacy, and identification of the mechanism of action and bioactive compounds) that can serve as a research template for high-throughput drug research.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"2"},"PeriodicalIF":4.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948237","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":"MAIT cells modulating the oral lichen planus immune microenvironment: a cellular crosstalk perspective.","authors":"Qian Mi, Xiaoli Wu, Yuhe Chen, Wenxia Meng","doi":"10.1007/s00011-024-01990-6","DOIUrl":"https://doi.org/10.1007/s00011-024-01990-6","url":null,"abstract":"<p><p>Mucosal-associated invariant T (MAIT) cells, a type of T lymphocytes with innate-like characteristics, are crucial in bridging innate and adaptive immunity. When activated, MAIT cells release various inflammatory molecules and swiftly respond to antigens. Notably, numerous studies highlight the significant impact of MAIT cells on tumors and various immune disorders by influencing the immune microenvironment. Oral lichen planus (OLP) is an immune-mediated inflammatory condition mainly involving T lymphocytes. Previous research primarily focused on T cells alone, neglecting the broader immune environment. However, there is a current growing recognition of the complex interactions among multiple immune cells and inflammatory factors in patients with OLP. This immune microenvironment comprises T lymphocytes, fibroblasts, keratinocytes, dendritic cells, macrophages, inflammation-related cytokines, and chemokines, orchestrating intricate interactions that contribute to OLP initiation and persistence. Therefore, this review consolidates current research on the interplay between MAIT cells and other immune cells within the OLP microenvironment. We also delve into potential mechanisms through which MAIT cells regulate inflammation in patients with OLP, aiming to further explore the role of MAIT cells in these patients.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"10"},"PeriodicalIF":4.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947931","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":"Editorial expression of concern: Monocytes and lymphocytes as active participants in the pathogenesis of experimental shock.","authors":"D Altavilla, F Squadrito, L Ammendolia, G Squadrito, G M Campo, P Canale, M Ioculano, C Musolino, A Alonci, A Sardella, G Urna, A Saitta, A P Caputi","doi":"10.1007/s00011-024-01930-4","DOIUrl":"10.1007/s00011-024-01930-4","url":null,"abstract":"","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"2281"},"PeriodicalIF":4.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139974","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":"Single-cell transcriptome analysis of the mouse lungs during the injury and recovery periods after lipopolysaccharide administration.","authors":"Hou-Ping Wang, Jian He, Jian-Rong He, Dan-Dan Li, He Huang, Bing Chen","doi":"10.1007/s00011-024-01951-z","DOIUrl":"10.1007/s00011-024-01951-z","url":null,"abstract":"<p><strong>Objective: </strong>This study sought to investigate the cellular and molecular alterations during the injury and recovery periods of ALI and develop effective treatments for ALI.</p><p><strong>Methods: </strong>Pulmonary histology at 1, 3, 6, and 9 days after lipopolysaccharide administration mice were assessed. An unbiased single-cell RNA sequencing was performed in alveoli tissues from injury (day 3) and recovery (day 6) mice after lipopolysaccharide administration. The roles of Fpr2 and Dpp4 in ALI were assessed.</p><p><strong>Results: </strong>The most severe lung injury occurred on day 3, followed by recovery entirely on day 9 after lipopolysaccharide administration. The numbers of Il1a⁺ neutrophils, monocytes/macrophages, and Cd4⁺ and Cd8⁺ T cells significantly increased at day 3 after LPS administration; subsequently, the number of Il1a⁺ neutrophils greatly decreased, the numbers of monocytes/macrophages and Cd4⁺ and Cd8⁺ T cells continuously increased, and the number of resident alveolar macrophages significantly increased at day 6. The interactions between monocytes/macrophages and pneumocytes during the injury period were enhanced by the Cxcl10/Dpp4 pair, and inhibiting Dpp4 improved ALI significantly, while inhibiting Fpr2 did not.</p><p><strong>Conclusions: </strong>Our results offer valuable insights into the cellular and molecular mechanisms underlying its progression and identify Dpp4 as an effective therapeutic target for ALI.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"2087-2107"},"PeriodicalIF":4.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390244","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":"Retraction Note: The role of nitric oxide during healing of trauma to the skeletal muscle.","authors":"Lidiane Isabel Filippin, María José Cuevas, Elena Lima, Norma Possa Marroni, Javier Gonzalez Gallego, Ricardo Machado Xavier","doi":"10.1007/s00011-024-01963-9","DOIUrl":"10.1007/s00011-024-01963-9","url":null,"abstract":"","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"2279"},"PeriodicalIF":4.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499587","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}