Inflammation最新文献

{"title":"Anti-IL-17 Inhibits PINK1/Parkin Autophagy and M1 Macrophage Polarization in Rheumatic Heart Disease.","authors":"Ling Bai, Yuan Li, Chuanghong Lu, Yiping Yang, Jie Zhang, Zirong Lu, Keke Huang, Shenglin Xian, Xi Yang, Na Na, Feng Huang, Zhiyu Zeng","doi":"10.1007/s10753-024-02094-3","DOIUrl":"10.1007/s10753-024-02094-3","url":null,"abstract":"<p><p>Rheumatic heart disease (RHD) is an important and preventable cause of cardiovascular death and disability, but the lack of clarity about its exact mechanisms makes it more difficult to find alternative methods or prevention and treatment. We previously demonstrated that increased IL-17 expression plays a crucial role in the development of RHD-related valvular inflammatory injury. Macrophage autophagy/polarization may be a pro-survival strategy in the initiation and resolution of the inflammatory process. This study investigated the mechanism by which IL-17 regulates autophagy/polarization activation in macrophages. A RHD rat model was generated, and the effects of anti-IL-17 and 3-methyladenine (3-MA) were analyzed. The molecular mechanisms underlying IL-17-induced macrophage autophagy/polarization were investigated via in vitro experiments. In our established RHD rat model, the activation of the macrophage PINK1/Parkin autophagic pathway in valve tissue was accompanied by M1 macrophage infiltration, and anti-IL-17 treatment inhibited autophagy and reversed macrophage inflammatory infiltration, thereby attenuating endothelial-mesenchymal transition (EndMT) in the valve tissue. The efficacy of 3-MA treatment was similar to that of anti-IL-17 treatment. Furthermore, in THP-1 cells, the pharmacological promotion of autophagy by IL-17 induced M1-type polarization, whereas the inhibition of autophagy by 3-MA reversed this process. Mechanistically, silencing PINK1 in THP-1 blocked autophagic flux. Moreover, IL-17-induced M1-polarized macrophages promoted EndMT in HUVECs. This study revealed that IL-17 plays an important role in EndMT in RHD via the PINK1/Parkin autophagic pathway and macrophage polarization, providing a potential therapeutic target.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"870-884"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM35 Negatively Regulates the cGAS-STING-Mediated Signaling Pathway by Attenuating K63-Linked Ubiquitination of STING.","authors":"Jikai Zhang, Yuhao Wu, Yiwen Wang, Jing Wang, Yinlin Ye, Hang Yin, Ningye Sun, Baoying Qin, Nan Sun","doi":"10.1007/s10753-024-02093-4","DOIUrl":"10.1007/s10753-024-02093-4","url":null,"abstract":"<p><p>The cGAS-STING-mediated antiviral response plays an important role in the defense against DNA virus infection. Tripartite motif protein 35 (TRIM35), an E3 ubiquitin ligase, was identified as a positive regulator of RLR-mediated antiviral signaling in our previous study, but the effect of TRIM35 on the cGAS-STING signaling pathway has not been elucidated. Herein, we showed that TRIM35 negatively regulates the cGAS-STING signaling pathway by directly targeting STING. TRIM35 overexpression significantly inhibited the cGAMP-triggered phosphorylation of TBK1 and IRF3, attenuating IFN-β expression and the downstream antiviral response. Mechanistically, TRIM35 colocalized and directly interacted with STING in the cytoplasm. TRM35 removed K63-linked ubiquitin from STING through the C36 and C44 sites in the RING domain, which impaired the interaction of STING with TBK1 or IKKε. In addition, we demonstrated that the RING domain is a key region for the antiviral effects of TIRM35. These results collectively indicate that TRIM35 negatively regulates type I interferon (IFN-I) production by targeting and deubiquitinating STING. TRIM35 may be a potential therapeutic target for controlling viral infection.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"855-869"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859599","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":"Dimethyloxallyl Glycine Preconditioning Promotes the Anti-inflammatory and Anti-fibrotic Effects of Human Umbilical Cord Mesenchymal Stem Cells on Kidney Damage in Systemic Lupus Erythematosus Related to TGF-β/Smad Signaling Pathway.","authors":"Anfeng Ning, Nansong Xiao, Xiaoqin Yu, Hu Wang, Chunyi Guan, Changlong Guo, Yichao Dong, Xu Ma, Hongfei Xia","doi":"10.1007/s10753-024-02092-5","DOIUrl":"10.1007/s10753-024-02092-5","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease lacking effective treatments without adverse effects. Dimethyloxallyl glycine (DMOG) enhanced mesenchymal stem cells (MSC) capabilities, but it remains unclear how DMOG-pretreatment of MSCs augments their SLE treatment. Here, we explore the therapeutic potential of DMOG-pretreated human umbilical cord MSCs (hUC-MSCs) in a mouse lupus nephritis (LN) model. In vitro experiments showed that DMOG could alleviate the mRNA levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-6 and increase the mRNA level of IL-13 in lipopolysaccharide (LPS)-induced inflammation in hUC-MSCs. DMOG enhanced the migratory and invasive abilities of the hUC-MSCs. In vivo animal studies revealed that DMOG-pretreated hUC-MSCs exhibited more pronounced inhibition of lymphadenectasis and reduced kidney weight and urinary protein content than MSCs alone. DMOG-pretreated hUC-MSCs improved renal morphological structure and alleviated inflammatory cell infiltration and renal fibrosis, evidenced by the reduced mRNA levels of fibrosis markers, including fibronectin (Fn), collagen alpha-1 chain (Colα1), collagen alpha-3 chain (Colα3), and TNF-α, IFN-γ, and IL-6 cytokines. Further investigation revealed that DMOG-pretreated hUC-MSCs down-regulated the expressions of transforming growth factor (Tgf)-β1 and its downstream effectors Smad2 and Smad3, recognized as central mediators in renal fibrosis (P < 0.05). The findings suggest that DMOG-pretreated hUC-MSCs can augment the therapeutic efficacy of hUC-MSCs in LN by enhancing their anti-inflammatory and antifibrotic effects, and the TGF-β/Smad signaling pathway may be involved in this process.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"839-854"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751622","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":"Methylprednisolone Modulates the Tfr/Tfh ratio in EAE-Induced Neuroinflammation through the PI3K/AKT/FoxO1 and PI3K/AKT/mTOR Signalling Pathways.","authors":"Nan Wu, Yun Zhao, Minjun Xiao, Hui Liu, Hongliang Chen, Bin Liu, Xuezhen Wang, Xueli Fan","doi":"10.1007/s10753-024-02099-y","DOIUrl":"10.1007/s10753-024-02099-y","url":null,"abstract":"<p><p>Methylprednisolone (MP) is a potent glucocorticoid that can effectively inhibit immune system inflammation and brain tissue damage in Multiple sclerosis (MS) patients. T follicular helper (Tfh) cells are a subpopulation of activated CD4 + T cells, while T follicular regulatory (Tfr) cells, a novel subset of Treg cells, possess specialized abilities to suppress the Tfh-GC response and inhibit antibody production. Dysregulation of either Tfh or Tfr cells has been implicated in the pathogenesis of MS. However, the molecular mechanism underlying the anti-inflammatory effects of MP therapy on experimental autoimmune encephalomyelitis (EAE), a representative model for MS, remains unclear. This study aimed to investigate the effects of MP treatment on EAE and elucidate the possible underlying molecular mechanisms involed. We evaluated the effects of MP on disease progression, CNS inflammatory cell infiltration and myelination, microglia and astrocyte activation, as well as Tfr/Tfh ratio and related molecules/inflammatory factors in EAE mice. Additionally, Western blotting was used to assess the expression of proteins associated with the PI3K/AKT pathway. Our findings demonstrated that MP treatment ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Furthermore, it reduced microglial and astrocytic activation. MP may increase the number of Tfr cells and the levels of cytokine TGF-β1, while reducing the number of Tfh cells and the levels of cytokine IL-21, as well as regulate the imbalanced Tfr/Tfh ratio in EAE mice. The PI3K/AKT/FoxO1 and PI3K/AKT/mTOR pathways were found to be involved in EAE development. However, MP treatment inhibited their activation. MP reduced neuroinflammation in EAE by regulating the balance between Tfr/Tfh cells via inhibition of the PI3K/AKT/FoxO1 and PI3K/AKT/mTOR signalling pathways.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"950-962"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-11 Is Involved in Hyperoxia-induced Bronchopulmonary Dysplasia in Newborn Mice by Mediating Epithelium-Fibroblast Cross-talk.","authors":"Haiyan Zhu, Rongrong Zhang, Tianping Bao, Mengmeng Ma, Jingyan Li, Linxia Cao, Bingrui Yu, Jian Hu, Zhaofang Tian","doi":"10.1007/s10753-024-02089-0","DOIUrl":"10.1007/s10753-024-02089-0","url":null,"abstract":"<p><strong>Background: </strong>Bronchopulmonary dysplasia (BPD) is a chronic lung disorder predominantly affecting preterm infants. Oxygen therapy, a common treatment for BPD, often leads to hyperoxia-induced pulmonary damage, particularly targeting alveolar epithelial cells (AECs). Crucially, disrupted lung epithelium-fibroblast interactions significantly contribute to BPD's pathogenesis. Previous studies on interleukin-11 (IL-11) in lung diseases have yielded conflicting results. Recent research, however, highlights IL-11 as a key regulator of fibrosis, stromal inflammation, and epithelial dysfunction. Despite this, the specific role of IL-11 in BPD remains underexplored. Our transcriptome analysis of normal and hyperoxia-exposed murine lung tissues revealed an increased expression of IL-11 RNA. This study aimed to investigate IL-11's role in modulating the disrupted interactions between AECs and fibroblasts in BPD.</p><p><strong>Methods: </strong>BPD was modeled in vivo by exposing C57BL/6J neonatal mice to hyperoxia. Histopathological changes in lung tissue were evaluated with hematoxylin-eosin staining, while lung fibrosis was assessed using Masson staining and immunohistochemistry (IHC). To investigate IL-11's role in pulmonary injury contributing to BPD, IL-11 levels were reduced through intraperitoneal administration of IL-11RαFc in hyperoxia-exposed mice. Additionally, MLE-12 cells subjected to 95% oxygen were collected and co-cultured with mouse pulmonary fibroblasts (MPFs) to measure α-SMA and Collagen I expression levels. IL-11 levels in the supernatants were quantified using an enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Both IHC and Masson staining revealed that inhibiting IL-11 expression alleviated pulmonary fibrosis in neonatal mice induced by hyperoxia, along with reducing the expression of fibrosis markers α-SMA and collagen I in lung tissue. In vitro analysis showed a significant increase in IL-11 levels in the supernatant of MLE-12 cells treated with hyperoxia. Silencing IL-11 expression in MLE-12 cells reduced α-SMA and collagen I concentrations in MPFs co-cultured with the supernatant of hyperoxia-treated MLE-12 cells. Additionally, ERK inhibitors decreased α-SMA and collagen I levels in MPFs co-cultured with the supernatant of hyperoxia-treated MLE-12 cells. Clinical studies found increased IL-11 levels in tracheal aspirates (TA) of infants with BPD.</p><p><strong>Conclusion: </strong>This research reveals that hyperoxia induces IL-11 secretion in lung epithelium. Additionally, IL-11 derived from lung epithelium emerged as a crucial mediator in myofibroblast differentiation via the ERK signaling pathway, highlighting its potential therapeutic value in BPD treatment.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"796-805"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751624","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":"Characteristics of Neonatal Sepsis and Predictive Values of Polyfunctional Assessment of Umbilical Cord Neutrophils Based on Single Cell Proteomic Secretion.","authors":"Yi Chen, Cheng Lu, Jiamin Huang, Linbin Li, Yunxi Yang, Yiming Shao, Lu Liu, Bingwei Sun","doi":"10.1007/s10753-024-02095-2","DOIUrl":"10.1007/s10753-024-02095-2","url":null,"abstract":"<p><p>The early diagnosis of neonatal sepsis is crucial as it remains a prevalent cause of neonatal mortality. In this study, we conducted an analysis on the clinical data and detection indicators of 22 cases with sepsis and 62 cases without sepsis among neonates. Our findings indicate that the clinical signs observed in neonates with sepsis lack specificity. In addition, the commonly used clinical inflammatory indicators (such as leukocyte count, neutrophil-to-lymphocyte ratio [NLR], C-reactive protein [CRP], procalcitonin) exhibit limited sensitivity and specificity. Furthermore, the current clinical measures lack the assessment of inflammatory factors. Therefore, in order to enhance the accuracy of early sepsis diagnosis in neonates, we have employed a novel microfluidic-based single-cell technology platform for the analysis of 32 cytokines secreted by neutrophils at the individual cell level under various toxin stimulation conditions. We have further investigated and compared the disparities in single-cell protein secretomics between umbilical cord blood neutrophils and healthy adult peripheral neutrophils within an in vitro sepsis model. Our findings indicate that in a resting state UCB neutrophils exhibited lower polyfunctionality compared with healthy adult blood neutrophils, and notable variations in cytokine secretion profiles were detected between the two groups. However, the polyfunctionality of UCB neutrophils significantly increased and surpassed that of healthy adult neutrophils when exposed to alpha-hemolysin or lipopolysaccharide. UCB neutrophils secreted a wide range of chemokines and inflammatory factors, among which GM-CSF and IL-18 were the most significant. Furthermore, we initially categorized the functional subgroups of neutrophils by considering the secretion of five primary cytokines by neutrophils (GM-CSF, IL-18, IL-8, MIP-1β, and MIF). The current study, for the first time, examined in detail the heterogeneity of protein secretion and the functional diversity of UCB neutrophils stimulated by different antigens. Moreover, new insight into neonatal sepsis, early diagnosis, and wider clinical applications of UCB neutrophils are provided by these data.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"885-901"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554667","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":"Sodium Houttuyfonate Ameliorates DSS-induced Colitis Aggravated by Candida albicans through Dectin-1/NF-κB/miR-32-5p/NFKBIZ Axis Based on Intestinal microRNA Profiling.","authors":"Chen Xu, Liu Yang, Ting Cheng, Zixu Wang, Chengcheng Liu, Jing Shao","doi":"10.1007/s10753-024-02091-6","DOIUrl":"10.1007/s10753-024-02091-6","url":null,"abstract":"<p><p>Our previous research indicated that Sodium houttuyfonate (SH) can effectively ameliorate dextran sulfate sodium (DSS)-induced colitis exacerbated by Candida albicans. However, the underlying protective mechanism of SH remains unclear. Therefore, in this study, a mice colitis model was infected with C. albicans, and the total colonic miRNAs were assessed. Furthermore, the differentially expressed miRNAs were enriched, clustered, and analyzed. Moreover, based on the dual luciferase analysis of NFKBIZ modulation by miR-32-5p, the in vitro and in vivo therapeutic effects of SH on inflammatory response, fungal burden, oxidative stress, and apoptosis were assessed at transcriptional and translational levels in the presence of agonist and antagonist. A total of 1157 miRNAs were identified, 84 of which were differentially expressed. Furthermore, qRT-PCR validated that SH treatment improved 17 differentially expressed miRNAs with > fourfold upregulation or > sixfold downregulation. Similar to most differentially altered miRNA, C. albicans significantly increased Dectin-1, NF-κB, TNF-α, IL-1β, IL-17A, and decreased miR-32-5p which negatively targeted NFKBIZ. In addition, SH treatment reduced inflammatory response and fungal burden in a colitis model with C. albicans infection. Further analyses indicated that in C. albicans infected Caco2 cells, SH inhibited fungal growth, oxidative stress, and apoptosis by increasing Dectin-1, NF-κB, NFKBIZ, TNF-α, IL-1β, IL-17A, and decreasing miR-32-5p. Therefore, SH can ameliorate the severity of colitis aggravated by C. albicans via the Dectin-1/NF-κB/miR-32-5p/NFKBIZ axis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"820-838"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497879","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":"Exploring Scopoletin's Therapeutic Efficacy in DSS-Induced Ulcerative Colitis: Insights into Inflammatory Pathways, Immune Modulation, and Microbial Dynamics.","authors":"Abdelrahim Alqudah, Esam Qnais, Omar Gammoh, Yousra Bseiso, Mohammed Wedyan, Mohammad Alqudah, Alaa A A Aljabali, Murtaza Tambuwala","doi":"10.1007/s10753-024-02048-9","DOIUrl":"10.1007/s10753-024-02048-9","url":null,"abstract":"<p><p>This study aimed to investigate the therapeutic potential of scopoletin in ulcerative colitis, with a primary focus on its impact on crucial inflammatory pathways and immune responses. A male mouse model of DSS-induced colitis was employed with six distinct groups: a control group, a group subjected to DSS only, three groups treated with varying scopoletin doses, and the final group treated with dexamethasone. The investigation included an assessment of the effects of scopoletin on colitis symptoms, including alterations in body weight, Disease Activity Index (DAI), and histopathological changes in colonic tissue. Furthermore, this study scrutinized the influence of scopoletin on cytokine production, PPARγ and NF-κB expression, NLRP3 inflammasome, and the composition of intestinal bacteria. Scopoletin treatment yielded noteworthy improvements in DSS-induced colitis in mice, as evidenced by reduced weight loss and colonic shortening (p < 0.05, < 0.01, respectively). It effectively diminished TNF-α, IL-1β, and IL-12 cytokine levels (p < 0.01, p < 0.05), attenuated NLRP3 inflammasome activation and the associated cytokine release (p < 0.05, p < 0.01), and modulated the immune response by elevating PPARγ expression while suppressing NF-κB pathway activation (p < 0.05, p < 0.01). Additionally, scopoletin induced alterations in the gut microbiota composition, augmenting beneficial Lactobacillus and Bifidobacteria while reducing E. coli (p < 0.05). It also enhanced tight junction proteins, signifying an improvement in the intestinal barrier integrity (p < 0.05, < 0.01). Scopoletin is a promising therapeutic agent for managing ulcerative colitis, showing benefits that extend beyond mere anti-inflammatory actions to encompass regulatory effects on gut microbiota and restoration of intestinal integrity.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"575-589"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crucial Roles of RSAD2/viperin in Immunomodulation, Mitochondrial Metabolism and Autoimmune Diseases.","authors":"Siyan Chen, Jiani Ye, Yinfang Lin, Wenxiu Chen, Shenghao Huang, Qianru Yang, Hengrong Qian, Sheng Gao, Chunyan Hua","doi":"10.1007/s10753-024-02076-5","DOIUrl":"10.1007/s10753-024-02076-5","url":null,"abstract":"<p><p>Autoimmune diseases are typically characterized by aberrant activation of immune system that leads to excessive inflammatory reactions and tissue damage. Nevertheless, precise targeted and efficient therapies are limited. Thus, studies into novel therapeutic targets for the management of autoimmune diseases are urgently needed. Radical S-adenosyl methionine domain-containing 2 (RSAD2) is an interferon-stimulated gene (ISG) renowned for the antiviral properties of the protein it encodes, named viperin. An increasing number of studies have underscored the new roles of RSAD2/viperin in immunomodulation and mitochondrial metabolism. Previous studies have shown that there is a complex interplay between RSAD2/vipeirn and mitochondria and that binding of the iron-sulfur (Fe-S) cluster is necessary for the involvement of viperin in mitochondrial metabolism. Viperin influences the proliferation and development of immune cells as well as inflammation via different signaling pathways. However, the function of RSAD2/viperin varies in different studies and a comprehensive overview of this emerging theme is lacking. This review will describe the characteristics of RSAD2/viperin, decipher its function in immunometabolic processes, and clarify the crosstalk between RSAD2/viperin and mitochondria. Furthermore, we emphasize the crucial roles of RSAD2 in autoimmune diseases and its potential application value.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"520-540"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440449","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":"Autophagy Regulation Attenuates Neuroinflammation and Cognitive Decline in an Alzheimer's Disease Mouse Model with Chronic Cerebral Hypoperfusion.","authors":"Qin Yang, Chengmin Yang, Hui Lv, Xingwu Zheng, Sanyin Mao, Ning Liu, Shenglong Mo, Bao Liao, Meiling Yang, Zhicheng Lu, Lina Tang, Xiaorui Huang, Chongdong Jian, Jingwei Shang","doi":"10.1007/s10753-024-02043-0","DOIUrl":"10.1007/s10753-024-02043-0","url":null,"abstract":"<p><p>This study investigates the role of autophagy regulation in modulating neuroinflammation and cognitive function in an Alzheimer's disease (AD) mouse model with chronic cerebral hypoperfusion (CCH). Using the APP23/PS1 mice plus CCH model, we examined the impact of autophagy regulation on cognitive function, neuroinflammation, and autophagic activity. Our results demonstrate significant cognitive impairments in AD mice, exacerbated by CCH, but mitigated by treatment with the autophagy inhibitor 3-methyladenine (3-MA). Dysregulation of autophagy-related proteins, accentuated by CCH, underscores the intricate relationship between cerebral blood flow and autophagy dysfunction in AD pathology. While 3-MA restored autophagic balance, rapamycin (RAPA) treatment did not induce significant changes, suggesting alternative therapeutic approaches are necessary. Dysregulated microglial polarization and neuroinflammation in AD+CCH were linked to cognitive decline, with 3-MA attenuating neuroinflammation. Furthermore, alterations in M2 microglial polarization and the levels of inflammatory markers NLRP3 and MCP1 were observed, with 3-MA treatment exhibiting potential anti-inflammatory effects. Our findings shed light on the crosstalk between autophagy and neuroinflammation in AD+CCH and suggest targeting autophagy as a promising strategy for mitigating neuroinflammation and cognitive decline in AD+CCH.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"541-556"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476544","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}