Inflammation最新文献

{"title":"USP30-AS1 Suppresses Colon Cancer Cell Inflammatory Response Through NF-κB/MYBBP1A Signaling.","authors":"Ruonan Wang, Xiaolin Li, Yapei Jiang, Haowei Zhang, Shiyue Yang, Weidong Xie, Naihan Xu","doi":"10.1007/s10753-024-02170-8","DOIUrl":"https://doi.org/10.1007/s10753-024-02170-8","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and poses a significant threat to human health. Recent studies have underscored the crucial role of aberrant expression of long non-coding RNAs (lncRNAs) in the initiation and progression of CRC. In this study we identified that lncRNA USP30-AS1 is significantly downregulated in colorectal cancer tissues, particularly in the advanced stages of the disease. This downregulation correlates with reduced survival rates among patients. Enrichment analysis of genes associated with USP30-AS1 indicates a strong association with inflammatory responses. Notably, pro-inflammatory stimuli, including lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α), were found to upregulate the expression of USP30-AS1. Functional assays demonstrated that the knockdown of USP30-AS1 resulted in increased degradation of IκBα protein and enhanced NF-κB transcriptional activity, as well as elevated expression levels of NF-κB downstream inflammatory molecules, including NLRP3, IL-1β, and IL-18. Conversely, ectopic expression of USP30-AS1 inhibited NF-κB transactivation. Mechanistically, USP30-AS1 interacts with MYBBP1A, a known regulator of NF-κB signaling. Notably, overexpression of MYBBP1A alleviated the stimulatory effect of USP30-AS1 knockdown on NF-κB activation. Collectively, these findings suggest that USP30-AS1 acts as a suppressor of colorectal cancer cell growth by modulating the MYBBP1A/NF-κB signaling pathway, thereby highlighting USP30-AS1 as a potential novel therapeutic target for colorectal cancer treatment.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of GDNF-Driven Macrophage-to-Myofibroblast Transition Protects Against Colitis-Associated Intestinal Fibrosis.","authors":"Jian Zeng, Xiao-Long Du, Qiong-Qiong Lu, Wan-Qun Chen, Xiao-Jun Yang","doi":"10.1007/s10753-024-02175-3","DOIUrl":"https://doi.org/10.1007/s10753-024-02175-3","url":null,"abstract":"<p><p>Glial cell line-derived neurotrophic factor (GDNF) has been demonstrated to promote the development of liver fibrosis, but its role in intestinal fibrosis is unknown. Macrophage-to-myofibroblast transition (MMT) is an important pathway contributing to fibrosis diseases. However, whether MMT cells, characterized by co-expressing both macrophage (CD68 or F4/80) and myofibroblast (α-SMA) markers, occurs in intestinal fibrosis remain to be addressed. Here, we showed that GDNF expression and the infiltration of MMT cells in intestinal tissues from patients with fibrostenotic Crohn's disease (CD) and a mouse model of chronic dextran sodium salt-induced intestinal fibrosis were significantly increased. GDNF induced bone marrow-derived macrophages (BMDMs) differentiation into MMT cells in vitro. Mechanistically, the Src pathway was activated by GDNF stimulation and contributed to GDNF-induced MMT in BMDMs. Moreover, pharmacological inhibition of GDNF by using antibody markedly decreased the infiltration of MMT cells following the decrease of collagen deposition and α-SMA and Col1 expression in the mouse model of colitis-associated intestinal fibrosis. In conclusion, GDNF is able to induce MMT and contributes to intestinal fibrosis in the context of chronic intestinal inflammation. Pharmacological inhibition of GDNF-driven MMT might provide a novel approach for the treatment of fibrosis complication in CD.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Machine Learning Identifies Key Gene PHLDA1 Suppressing NAFLD Progression.","authors":"Zhenwei Yang, Zhiqin Chen, Jingchao Wang, Yizhang Li, Hailin Zhang, Yu Xiang, Yuwei Zhang, Zhaozhao Shao, Pei Wu, Ding Lu, Huajiang Lin, Zhaowei Tong, Jiang Liu, Quan Dong","doi":"10.1007/s10753-024-02164-6","DOIUrl":"https://doi.org/10.1007/s10753-024-02164-6","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) poses a serious global health threat, with its progression mechanisms not yet fully understood. While several molecular markers for NAFLD have been developed in recent years, a lack of robust evidence hampers their clinical application. Therefore, identifying novel and potent biomarkers would directly aid in the prediction, prevention, and personalized treatment of NAFLD. We downloaded NAFLD-related datasets from the Gene Expression Omnibus (GEO). Differential expression analysis and functional analysis were initially conducted. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) and multiple machine learning strategies were employed to screen and identify key genes, and the diagnostic value was assessed using Receiver Operating Characteristic (ROC) analysis. We then explored the relationship between genes and immune cells using transcriptome data and single-cell RNA sequencing (scRNA-seq) data. Finally, we validated our findings in cell and mouse NAFLD models. We obtained 23 overlapping differentially expressed genes (DEGs) across three NAFLD datasets. Enrichment analysis revealed that DEGs were associated with Apoptosis, Parathyroid hormone synthesis, secretion and action, Colorectal cancer, p53 signaling pathway, and Biosynthesis of unsaturated fatty acids. After employing machine learning strategies, we identified one gene, pleckstrin homology like domain family A member 1 (PHLDA1), downregulated in NAFLD and showing high diagnostic accuracy. CIBERSORT analysis revealed significant associations of PHLDA1 with various immune cells. Single-cell data analysis demonstrated downregulation of PHLDA1 in NAFLD, with PHLDA1 exhibiting a significant negative correlation with macrophages. Furthermore, we found PHLDA1 to be downregulated in an in vitro hepatic steatosis cell model, and overexpression of PHLDA1 significantly reduced lipid accumulation, as well as the expression of key molecules involved in hepatic lipogenesis and fatty acid uptake, such as FASN, SCD-1, and CD36. Additionally, gene set enrichment analysis (GSEA) pathway enrichment analysis suggested that PHLDA1 may influence NAFLD progression through pathways such as Cytokine Cytokine Receptor Interaction, Ecm Receptor Interaction, Parkinson's Disease, and Ribosome pathways. Our conclusions were further validated in a mouse model of NAFLD. Our study reveals that PHLDA1 inhibits the progression of NAFLD, as overexpression of PHLDA1 significantly reduces lipid accumulation in cells and markedly decreases the expression of key molecules involved in liver lipogenesis and fatty acid uptake. Therefore, PHLDA1 may emerge as a novel potential target for future prediction, diagnosis, and targeted prevention of NAFLD.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GZMK Facilitates Experimental Rheumatoid Arthritis Progression by Interacting with CCL5 and Activating the ERK Signaling.","authors":"Liting Xu, Hui Wang, Congcong Sun, Qingyu Zhao, Lili Wang, Qianqian Yan, Jialin Wang, Na Lin, Chunfang Liu","doi":"10.1007/s10753-024-02166-4","DOIUrl":"https://doi.org/10.1007/s10753-024-02166-4","url":null,"abstract":"<p><p>Synovial over-proliferation is a key event in the progression of rheumatoid arthritis (RA) disease. Ferroptosis may be essential for maintaining the balance between synovial proliferation and death. This study aimed to investigate the molecular mechanisms mediating the activation and ferroptosis of collagen-induced arthritis (CIA)-synovial fibroblasts (SFs). Differentially expressed genes (DEGs) in the synovial tissues of CIA rats and normal rats were screened through sequencing. The GSE115662 dataset from the GEO database was analyzed and screened for DEGs. The viability, proliferation, migration, invasion, cell cycle, and apoptosis of CIA-SFs were analyzed by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, transwell migration, and invasion assays. The ferroptosis of CIA-SFs was assessed using matching reagent kits to detect indicators like reactive oxygen species, ferrous iron, malondialdehyde, glutathione, and superoxide dismutase. The interaction between Granzyme K (GZMK) and C-C motif chemokine 5 (CCL5) was determined by coimmunoprecipitation assay. We found abnormal GZMK expression in the GSE115662 database and mRNA sequencing data. GZMK was overexpressed in CIA-SFs, and GZMK promoted cell proliferation, migration, invasion, inflammation, and decreased cell apoptosis and ferroptosis in CIA-SFs. GZMK could interact with CCL5 to activate the ERK signaling. GZMK and CCL5 knockdown improved by reducing arthritis scores, redness and swelling of paws, and pathological changes in joint synovium of CIA rats. CCL5 overexpression reversed the effects of GZMK silencing on CIA-SFs cell proliferation, migration, invasion, apoptosis, and ferroptosis. We confirmed that GZMK accelerated experimental rheumatoid arthritis progression by interacting with CCL5 and activating the ERK signaling.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetyl 11-Keto Beta-Boswellic Acid Improves Neurological Functions in a Mouse Model of Multiple Sclerosis.","authors":"Saeed Karima, Seyyed Hossein Khatami, Sajad Ehtiati, Sara Khoshtinatnikkhouy, Reza Ataei Kachouei, Ali Jahanbazi Jahan-Abad, Abbas Tafakhori, Hadis Firoozpour, Farzaneh Salmani","doi":"10.1007/s10753-024-02176-2","DOIUrl":"https://doi.org/10.1007/s10753-024-02176-2","url":null,"abstract":"<p><p>Acetyl-11-keto-β-boswellic acid is one of the main active components of Boswellia sp. resin with the most potent anti-inflammatory activity. In recent years, herbal therapy has received considerable attention for the treatments of inflammatory and demyelinating diseases such as Multiple sclerosis (MS). Studies have shown that herbal compounds could enhance myelin repair and suppress inflammation. This study was designed to investigate the therapeutic effects of intraperitoneal administration of AKBA in Experimental Autoimmune Encephalomyelitis (EAE), as an animal model of MS. Following EAE induction in female C57BL/6J mice, animals were treated with AKBA and the levels of different serum inflammatory mediators, as well as motor functions, myelination, and inflammatory cell infiltration were assessed. Our results revealed that the application of AKBA alleviated EAE clinical severity, and suppressed inflammation, demyelination, leukocyte infiltration, and gliosis in EAE mice. Our findings suggest that the therapeutic effects of AKBA are likely a consequence of its neuroprotective and anti-inflammatory properties. The beneficial effects of AKBA may therefore provide new insights in various neuroinflammatory diseases such as MS and thereby could serve as a potential treatment candidate.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atorvastatin Alleviates Age-Related Macular Degeneration via AIM2-Regulated Pyroptosis.","authors":"Jing Lu, Yuxia He, Yong Du, Long Zhao, Ping Wu, Qinxin Shu, Hui Peng, Xing Wang","doi":"10.1007/s10753-024-02179-z","DOIUrl":"10.1007/s10753-024-02179-z","url":null,"abstract":"<p><p>The underlying causes of age-related macular degeneration (AMD) remain elusive and treatment options of it are limited, while atorvastatin (AT) is expected to improve AMD. Our study sought to uncover the specific mechanisms that initiate pyroptosis in AMD and elucidate whether AT ameliorates Aβ1-40-induced retinal damage by inhibiting pyroptosis. An animal model of AMD was triggered by Aβ1-40, and the therapeutic efficacy of AT was evaluated by hematoxylin and eosin staining (H&E), Optical Coherence Tomography (OCT), Electroretinogram (ERG) and other methods. Utilizing network pharmacology in conjunction with transcriptomics, we identified potential therapeutic pathways. we employed Western blotting (WB) and quantitative real-time PCR (qPCR) methodologies to evaluate the levels of pyroptosis. In vitro system of retinal pigment epithelium (RPE) cells injury was caused by Aβ1-40 and subsequently treated with AT or JC2-11. The extent of pyroptosis was quantified using enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and WB. Cell morphological changes were examined using light microscopy and scanning electron microscopy. Network pharmacology and transcriptomics identified AIM2/Caspase-1/GSDMD as the key pathway. AT improved the retinal morphological and functional damage caused by Aβ1-40, and decreased the production of AIM2, Asc, Caspase-1, GSDMD-N, Cleaved Caspase-1 and cytokines to exert an anti-inflammatory effect. In addition, AT improved the ruptured membrane of RPE cells caused by Aβ1-40. The use of JC2-11 further demonstrated that AT inhibits pyroptosis of RPE via AIM2/Caspase-1/GSDMD pathway activated by Aβ1-40. These discoveries illuminate the retinal conservation role of AT by effectively hindering the progression of pyroptosis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinamide N-oxide Inhibits Microglial Pyroptosis by Upregulating Mitophagy and Alleviates Neural Damage in Rats after TBI.","authors":"Xiaoyan Li, Lan Luo, Pengyu Duan, Yonghong Bi, Yao Meng, Xiaoqian Zhang, Weiyu Feng, Zhehao Jin, Kun Zuo, Xiangcheng Zhao, Bing Zhang","doi":"10.1007/s10753-024-02171-7","DOIUrl":"https://doi.org/10.1007/s10753-024-02171-7","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a severe injury characterized by neuroinflammation and oxidative stress. NAMO (Nicotinamide n-oxide) has anti-inflammatory and inhibits microglial overactivation in neurological disorders. However, the role and mechanism of NAMO in microglial pyroptosis after TBI are unknown. The aim of this study was to investigate the effects of NAMO on TBI and its potential mechanisms through in vivo and in vitro models. In this study, western blot assays were performed by extracting brain tissue mitochondria, and the results showed that NAMO promoted the expression of mitophagy-associated proteins (p62, LC3B, and TOMM20), reduced ROS levels, and inhibited pyroptosis-associated proteins (NLRP3, GSDMD, GSDMD-N, and Caspase-1) and inflammatory cytokines (IL-1β and IL-18). We followed up with immunofluorescence co-localization of GSDMD and IBA 1, which showed that NAMO inhibited microglial pyroptosis. In addition, NAMO promoted neurological recovery after TBI. In vitro experiments showed that NAMO upregulated mitophagy, improved mitochondrial dysfunction, and reduced ROS levels in microglia following lipopolysaccharide (LPS) + adenosine triphosphate (ATP) stimulation in HMC3 cells. We also found that NAMO inhibited pyroptosis-related proteins. To further illustrate whether NAMO affects pyroptosis through mitophagy, we applied the mitophagy inhibitor Mdivi-1 in both in vivo and in vitro models. The results showed that Mdivi-1 reversed NAMO's inhibitory effect on microglial pyroptosis. Taken together, our findings demonstrate that NAMO improves neurological recovery by inhibiting microglial pyroptosis through upregulation of mitophagy, suggesting that NAMO could be a potential therapeutic agent for TBI.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Inhibition of Phosphoglycerate Kinase 1 Reduces OxiDative Stress and Restores Impaired Autophagy in Experimental Acute Pancreatitis.","authors":"Lin Chen, Zhihao Wang, Yuyan Zhang, Qingtian Zhu, Guotao Lu, Xiaowu Dong, Jiajia Pan, Keyan Wu, Weijuan Gong, Weiming Xiao, Yanbing Ding, Yanyan Zhang, Yaodong Wang","doi":"10.1007/s10753-024-02173-5","DOIUrl":"https://doi.org/10.1007/s10753-024-02173-5","url":null,"abstract":"<p><p>Damage to pancreatic acinar cells (PAC) and intracellular metabolic disturbances play crucial roles in pancreatic necrosis during acute pancreatitis (AP). Phosphoglycerate kinase 1 (PGK1) is a crucial catalytic enzyme in glycolysis. However, the impact of PGK1-involving glycolysis in regulating metabolic necrosis in AP is unclear. Transcriptome analysis of pancreatic tissues revealed significant changes in the glycolysis pathway and PGK1 which positively correlated with the inflammatory response and oxidative stress injury in AP mice. Furthermore, we observed a substantial increase in PGK1 expression in damaged PAC, positively correlating with PAC necrosis. Treatment with NG52, a specific PGK1 inhibitor, ameliorated pancreatic necrosis, inflammatory damage, and oxidative stress. Transcriptomic data before and after NG52 treatment along with the Programmed Cell Death database confirmed that NG52 protected against PAC damage by rescuing impaired autophagy in AP. Additionally, the protective effect of NG52 was validated following pancreatic duct ligation. These findings underscore the involvement of PGK1 in AP pathogenesis, highlighting that PGK1 inhibition can mitigate AP-induced pancreatic necrosis, attenuate inflammatory and oxidative stress injury, and rescue impaired autophagy. Thus, the study findings suggest a promising interventional target for pancreatic necrosis, offering novel strategies for therapeutic approaches to clinical AP.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Key Genes Related to Immune-Lipid Metabolism in Skin Barrier Damage and Analysis of Immune Infiltration.","authors":"Ying Tu, Hua Gu, Na Li, Dongjie Sun, Zhenghui Yang, Li He","doi":"10.1007/s10753-024-02174-4","DOIUrl":"https://doi.org/10.1007/s10753-024-02174-4","url":null,"abstract":"<p><p>Several physical and chemical factors regulate skin barrier function. Skin barrier dysfunction causes many inflammatory skin diseases, such as atopic dermatitis and psoriasis. Activation of the immune response may lead to damage to the epidermal barrier. Abnormal lipid metabolism is defined as abnormally high or low values of plasma lipid components such as plasma cholesterol and triglycerides. The mouse skin barrier damage model was used for RNA sequencing. Bioinformatics analysis and validation were performed. Differently expressed genes (DEGs) related to immune and lipid metabolism were screened by differentially expressed gene analysis, and the enriched biological processes and pathways of these genes were identified by GO-KEGG. The interactions between DEGs were confirmed by constructing a PPI network. GSEA, transcription factor regulatory network, and immune infiltration analyses were performed for the 10 genes. Expression validation was performed by public datasets. The expression of key genes in mouse skin tissue was detected by qPCR. The expression of differentially expressed immune cell markers in the skin was detected by immunofluorescence. Based on the trans epidermal water loss (TEWL) score, the expression of key genes was detected by qPCR before skin barrier injury, at 4h and 7d, and at recovery from injury. Il17a, Il6, Tnf, Itgam, and Cxcl1 were immune-related key genes. Pla2g2f, Ptgs2, Plb1, Pla2g3, and Pla2g2d were key genes for lipid metabolism. Database validation and experimental results revealed that the expression trends of these genes were consistent with our analyses. The research value of these genes has been demonstrated through mouse datasets and experimental validation, and future therapeutic approaches may be able to mitigate the disease by targeting these genes to modulate the function of the skin barrier.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing Non-T2 Asthma: Key Pathways and Molecular Implications Indicative of Attenuated Th2 Response.","authors":"Jyh-Hong Lee, Yao-Hsu Yang, Yu-Tsan Lin, Li-Chieh Wang, Hsin-Hui Yu, Ya-Chiao Hu, Bor-Luen Chiang","doi":"10.1007/s10753-024-02159-3","DOIUrl":"https://doi.org/10.1007/s10753-024-02159-3","url":null,"abstract":"<p><p>Non-Type 2 (non-T2) asthma is characterized by a lack of allergic sensitization and normal to low total IgE levels. We aimed to explore molecular mechanisms and pathways differentiating non-T2 from T2-high pediatric asthma. We analyzed peripheral blood RNA samples from 11 non-T2 and 17 T2-high pediatric asthma patients using bulk RNA sequencing. Differentially expressed genes (DEGs) were identified, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and Protein-Protein Interaction (PPI) network construction. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were employed to explore significance of these DEGs. We utilized independent public datasets GSE145505 to validate our findings. We investigated Th cytokine profiles in an independent cohort of pediatric patients with non-T2 asthma (n = 38) and T2-high asthma (n = 64). We demonstrated that the total serum IgE levels of children with non-T2 asthma (128.4 ± 159.5 IU/mL) was significantly lower than that of those with T2-high asthma (405.8 ± 252.1 IU/mL). Our analysis revealed 136 DEGs distinguishing non-T2 from T2-high asthma. IPA identified predicted inhibition of IgE-FcεRI signaling pathways in non-T2 asthma. Our DEG data showed the expression of IGHV4-39, IGLV1-40, IGLV1-47, IGLV1-44, IGHV1-69, IGLV6-57, IGLV3-19, IGLV3-1, and IGLC7 were downregulated in our non-T2 asthma patient. The non-T2 group exhibited significantly higher concentrations of IL-2, IFN-γ, IL-6, and IL-17A compared to the T2-high group. Our integrated analysis differentiated non-T2 from T2-high asthma by revealing downregulation of specific immunoglobulin genes influencing FcεRI signaling, elevated Th1 cytokines and Th17 cytokines might affect IgE associated sensitization and alter Th2 allergic response.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}