Inflammation最新文献_第5页

Specific Knockdown of the NDUFS4 Gene Reveals Important Roles of Ferroptosis in UVB-induced Photoaging. 特异性敲除 NDUFS4 基因揭示了铁蛋白沉积在紫外线诱导的光老化中的重要作用

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-01 Epub Date: 2024-05-26 DOI: 10.1007/s10753-024-02057-8

Yan Teng, Hong Cui, Danfeng Xu, Hui Tang, Yu Gu, Yi Tang, Xiaohua Tao, Youming Huang, Yibin Fan

{"title":"Specific Knockdown of the NDUFS4 Gene Reveals Important Roles of Ferroptosis in UVB-induced Photoaging.","authors":"Yan Teng, Hong Cui, Danfeng Xu, Hui Tang, Yu Gu, Yi Tang, Xiaohua Tao, Youming Huang, Yibin Fan","doi":"10.1007/s10753-024-02057-8","DOIUrl":"10.1007/s10753-024-02057-8","url":null,"abstract":"Ultraviolet (UV) irradiation significantly contributes to photoaging. Ferroptosis, an iron-dependent cell death mode recently identified, plays a key role in UVB-induced skin photoaging. This study examines the functions and regulatory mechanisms of ferroptosis in this regard. Characterized by increased intracellular iron and reactive oxygen species (ROS), ferroptosis is associated with mitochondrial function and structure. Through RNA sequencing, we identified NADH: ubiquinone oxidoreductase subunit S4 (NDUFS4), a gene implicated in UVB-mediated photoaging, and explored its role in ferroptosis by NDUFS4 knockdown. In vitro, inhibiting NDUFS4 reduced ferroptosis, decreased ROS and matrix metallopeptidase 1 levels, and increased collagen type I alpha 1 chain, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1, and solute carrier family 7 member 11 levels, suggesting a reinforced ferroptosis protective mechanism. Additionally, NDUFS4 regulates ferroptosis via the mitogen-activated protein kinase (MAPK) pathway, with its knockdown reducing p38 and ERK phosphorylation and elevating GPX4 levels, enhancing ferroptosis resistance. Animal experiments supported these findings, demonstrating that Ferrostatin-1, a ferroptosis inhibitor, significantly mitigated UVB-induced skin photoaging and related protein expression. This study uncovers NDUFS4's novel role in regulating ferroptosis and provides new insights into ferroptosis-mediated UVB-induced skin photoaging.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"223-235"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154646","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}

引用次数: 0

N-Acetylcysteine Alleviates Necrotizing Enterocolitis by Depressing SESN2 Expression to Inhibit Ferroptosis in Intestinal Epithelial Cells. N-乙酰半胱氨酸通过抑制 SESN2 的表达来抑制肠上皮细胞的铁凋亡，从而缓解坏死性小肠结肠炎。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-01 Epub Date: 2024-07-22 DOI: 10.1007/s10753-024-02068-5

Chuchu Gao, Lixia Wang, Kai Fu, Shan Cheng, Sannan Wang, Zongtai Feng, Shenglin Yu, Zuming Yang

{"title":"N-Acetylcysteine Alleviates Necrotizing Enterocolitis by Depressing SESN2 Expression to Inhibit Ferroptosis in Intestinal Epithelial Cells.","authors":"Chuchu Gao, Lixia Wang, Kai Fu, Shan Cheng, Sannan Wang, Zongtai Feng, Shenglin Yu, Zuming Yang","doi":"10.1007/s10753-024-02068-5","DOIUrl":"10.1007/s10753-024-02068-5","url":null,"abstract":"Abstract-Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in neonates, and effective strategies to prevent and treat NEC are still lacking. Studies have shown that N-acetylcysteine (NAC) has protective effects against NEC, however, the specific mechanism underlying its effects on intestinal functions remains unclear. Recently, NAC has been shown to suppress ferroptosis in many diseases, while it is unclear whether the beneficial effects of NAC on NEC are related to ferroptosis. In this study, we revealed that ferroptosis was significantly induced in intestinal samples from infants with NEC. NAC alleviated intestinal inflammation, barrier damage and ferroptosis in multifactorial NEC models in vivo and in vitro. Sestrin2 (SESN2) was identified as an important mediator of NAC-induced ferroptosis resistance in intestinal epithelial cells. Furthermore, SESN2 knockdown inhibited the inflammatory response, alleviated barrier damage and ferroptosis in intestinal epithelial cells and enhanced the protective effects of NAC to a certain extent. Conversely, cells overexpressing SESN2 showed the opposite changes. In summary, our study demonstrated that NAC attenuates NEC progression by decreasing SESN2 expression to inhibit ferroptosis in intestinal epithelial cells, suggesting that NAC might be an effective clinical treatment for NEC.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"464-482"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733985","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}

引用次数: 0

4-Octyl Itaconate Attenuates Neuroinflammation in Experimental Autoimmune Encephalomyelitis Via Regulating Microglia. 伊他康酸 4-辛酯通过调节小胶质细胞减轻实验性自身免疫性脑脊髓炎的神经炎症反应

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-01 Epub Date: 2024-05-18 DOI: 10.1007/s10753-024-02050-1

Ning Zhao, Ming Yi, Lin-Jie Zhang, Qiu-Xia Zhang, Li Yang

{"title":"4-Octyl Itaconate Attenuates Neuroinflammation in Experimental Autoimmune Encephalomyelitis Via Regulating Microglia.","authors":"Ning Zhao, Ming Yi, Lin-Jie Zhang, Qiu-Xia Zhang, Li Yang","doi":"10.1007/s10753-024-02050-1","DOIUrl":"10.1007/s10753-024-02050-1","url":null,"abstract":"Abnormal activation of microglia, the resident macrophages in the central nervous system, plays an important role in the pathogenesis of multiple sclerosis (MS). The immune responsive gene 1(IRG1)/itaconate axis is involved in regulating microglia-mediated neuroinflammation. 4-Octyl itaconate (4-OI), a derivative of itaconate, plays a crucial immunomodulatory role in macrophages. This study investigated the effects and mechanisms of action of 4-OI on experimental autoimmune encephalomyelitis (EAE) and inflammatory BV2 microglia. In an EAE mouse model, clinical evaluation was conducted during the disease course. Hematoxylin and eosin staining was performed to assess inflammatory infiltration and Luxol Fast Blue was used to visualize pathological damage. Quantitative real-time polymerase chain reaction, western blotting and immunofluorescence were used to evaluate inflammatory response and microglial function status in EAE mice. BV2 microglia were used to further investigate the effects and mechanisms of action of 4-OI in vitro. 4-OI significantly alleviated the clinical symptoms of EAE, the inflammatory infiltration, and demyelination; reduced the levels of inflammatory factors; and inhibited the classical activation of microglia in the spinal cord. 4-OI successfully suppressed the classical activation of BV2 microglia and decreased the levels of inflammatory factors by activating the Nrf2/HO-1 signaling pathway. Furthermore, 4-OI downregulated IRG1 expression in both EAE mice and inflammatory BV2 microglia. 4-OI attenuates the microglia-mediated neuroinflammation and has promising therapeutic effects in MS.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"151-164"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957256","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}

引用次数: 0

Periodontopathogen-Related Cell Autophagy-A Double-Edged Sword. 牙周病原体相关细胞自噬--一把双刃剑

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-01 Epub Date: 2024-05-19 DOI: 10.1007/s10753-024-02049-8

Li Ma, Zhengguo Cao

{"title":"Periodontopathogen-Related Cell Autophagy-A Double-Edged Sword.","authors":"Li Ma, Zhengguo Cao","doi":"10.1007/s10753-024-02049-8","DOIUrl":"10.1007/s10753-024-02049-8","url":null,"abstract":"The periodontium is a highly organized ecosystem, and the imbalance between oral microorganisms and host defense leads to periodontal diseases. The periodontal pathogens, mainly Gram-negative anaerobic bacteria, colonize the periodontal niches or enter the blood circulation, resulting in periodontal tissue destruction and distal organ damage. This phenomenon links periodontitis with various systemic conditions, including cardiovascular diseases, malignant tumors, steatohepatitis, and Alzheimer's disease. Autophagy is an evolutionarily conserved cellular self-degradation process essential for eliminating internalized pathogens. Nowadays, increasing studies have been carried out in cells derived from periodontal tissues, immune system, and distant organs to investigate the relationship between periodontal pathogen infection and autophagy-related activities. On one hand, as a vital part of innate and adaptive immunity, autophagy actively participates in host resistance to periodontal bacterial infection. On the other, certain periodontal pathogens exploit autophagic vesicles or pathways to evade immune surveillance, therefore achieving survival within host cells. This review provides an overview of the autophagy process and focuses on periodontopathogen-related autophagy and their involvements in cells of different tissue origins, so as to comprehensively understand the role of autophagy in the occurrence and development of periodontal diseases and various periodontitis-associated systemic illnesses.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1-14"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957259","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}

引用次数: 0

Celastrol Regulates the Hsp90-NLRP3 Interaction to Alleviate Rheumatoid Arthritis. Celastrol 调节 Hsp90-NLRP3 相互作用以缓解类风湿关节炎。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-01 Epub Date: 2024-06-14 DOI: 10.1007/s10753-024-02060-z

Junjie Yang, Biyao He, Longjiao Dang, Jiayu Liu, Guohao Liu, Yuwei Zhao, Pengfei Yu, Qiaoyun Wang, Lei Wang, Wenyu Xin

{"title":"Celastrol Regulates the Hsp90-NLRP3 Interaction to Alleviate Rheumatoid Arthritis.","authors":"Junjie Yang, Biyao He, Longjiao Dang, Jiayu Liu, Guohao Liu, Yuwei Zhao, Pengfei Yu, Qiaoyun Wang, Lei Wang, Wenyu Xin","doi":"10.1007/s10753-024-02060-z","DOIUrl":"10.1007/s10753-024-02060-z","url":null,"abstract":"Previous studies have verified that celastrol (Cel) protects against rheumatoid arthritis (RA) by inhibiting the NLRP3 inflammasome signaling pathway, but the molecular mechanism by which Cel regulates NLRP3 has not been clarified. This study explored the specific mechanisms of Cel in vitro and in vivo. A type II collagen-induced arthritis (CIA) mouse model was used to study the antiarthritic activity of Cel; analysis of paw swelling, determination of the arthritis score, and pathological examinations were performed. The antiproliferative and antimigratory effects of Cel on TNF-α induced fibroblast-like synoviocytes (FLSs) were tested. Proinflammatory factors were evaluated using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB/NLRP3 pathway components was determined by western blotting and immunofluorescence staining in vitro and in vivo. The putative binding sites between Cel and Hsp90 were predicted through molecular docking, and the binding interactions were determined using the Octet RED96 system and coimmunoprecipitation. Cel decreased arthritis severity and reduced TNF-α-induced FLSs migration and proliferation. Additionally, Cel inhibited NF-κB/NLRP3 signaling pathway activation, reactive oxygen species (ROS) production, and proinflammatory cytokine secretion. Furthermore, Cel interacted directly with Hsp90 and blocked the interaction between Hsp90 and NLRP3 in FLSs. Our findings revealed that Cel regulates NLRP3 inflammasome signaling pathways both in vivo and in vitro. These effects are induced through FLSs inhibition of the proliferation and migration by blocking the interaction between Hsp90 and NLRP3.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"346-360"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317018","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}

引用次数: 0

AMPK Regulates M1 Macrophage Polarization through the JAK2/STAT3 Signaling Pathway to Attenuate Airway Inflammation in Obesity-Related Asthma. AMPK通过JAK2/STAT3信号通路调节M1巨噬细胞极化，从而减轻肥胖相关性哮喘的气道炎症。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-01 Epub Date: 2024-06-17 DOI: 10.1007/s10753-024-02070-x

Jiahui Lei, Zhenhui Shu, He Zhu, Limin Zhao

{"title":"AMPK Regulates M1 Macrophage Polarization through the JAK2/STAT3 Signaling Pathway to Attenuate Airway Inflammation in Obesity-Related Asthma.","authors":"Jiahui Lei, Zhenhui Shu, He Zhu, Limin Zhao","doi":"10.1007/s10753-024-02070-x","DOIUrl":"10.1007/s10753-024-02070-x","url":null,"abstract":"Abstract-Obesity-related asthma is primarily characterized by nonallergic inflammation, with pathogenesis involving oxidative stress, metabolic imbalance, and immunoinflammatory mechanisms. M1 macrophages, which predominantly secrete pro-inflammatory factors, mediate insulin resistance and systemic metabolic inflammation in obese individuals. Concurrently, adenosine monophosphate-activated protein kinase (AMPK) serves as a critical regulator of intracellular energy metabolism and is closely associated with macrophage activation. However, their specific roles and associated mechanisms in obesity-related asthma remain to be explored. In this study, we investigated the macrophage polarization status and potential interventional mechanisms through obesity-related asthmatic models and lipopolysaccharide (LPS) -treated RAW264.7 cell with a comprehensive series of evaluations, including HE, PAS and Masson staining of lung histopathology, immunohistochemical staining, immunofluorescence technology, qRT-PCR, Western Blot, and ELISA inflammatory factor analysis. The results revealed M1 macrophage polarization in obesity-related asthmatic lung tissue alongside downregulation of AMPK expression. Under LPS stimulation, exogenous AMPK activation attenuated M1 macrophage polarization via the Janus kinase 2/ signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Additionally, in obesity-related asthmatic mice, AMPK activation was found to alleviate airway inflammation by regulating M1 macrophage polarization, the mechanism closely associated with the JAK2/STAT3 pathway. These findings not only advance our understanding of macrophage polarization in obesity-related asthma, but also provide new therapeutic targets for its treatment.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"372-392"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418780","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}

引用次数: 0

RGS1 Enhancer RNA Promotes Gene Transcription by Recruiting Transcription Factor FOXJ3 and Facilitates Osteoclastogenesis Through PLC-IP3R-dependent Ca²⁺ Response in Rheumatoid Arthritis. RGS1 Enhancer RNA 通过招募转录因子 FOXJ3 促进基因转录，并通过 PLC-IP3R 依赖性 Ca2+ 响应促进类风湿关节炎的破骨细胞生成。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-01 Epub Date: 2024-06-21 DOI: 10.1007/s10753-024-02067-6

Lin Yuan, Nan Jiang, Yuxuan Li, Xin Wang, Wei Wang

{"title":"RGS1 Enhancer RNA Promotes Gene Transcription by Recruiting Transcription Factor FOXJ3 and Facilitates Osteoclastogenesis Through PLC-IP3R-dependent Ca2+ Response in Rheumatoid Arthritis.","authors":"Lin Yuan, Nan Jiang, Yuxuan Li, Xin Wang, Wei Wang","doi":"10.1007/s10753-024-02067-6","DOIUrl":"10.1007/s10753-024-02067-6","url":null,"abstract":"Recent evidence has highlighted the functions of enhancers in modulating transcriptional machinery and affecting the development of human diseases including rheumatoid arthritis (RA). Enhancer RNAs (eRNAs) are RNA molecules transcribed from active enhancer regions. This study investigates the specific function of eRNA in gene transcription and osteoclastogenesis in RA. Regulator of G protein signaling 1 (RGS1)-associated eRNA was highly activated in osteoclasts according to bioinformatics prediction. RGS1 mRNA was increased in mice with collagen-induced arthritis as well as in M-CSF/soluble RANKL-stimulated macrophages (derived from monocytes). This was ascribed to increased RGS1 eRNA activity. Silencing of 5'-eRNA blocked the binding between forkhead box J3 (FOXJ3) and the RGS1 promoter, thus suppressing RGS1 transcription. RGS1 accelerated osteoclastogenesis through PLC-IP3R-dependent Ca2+ response. Knockdown of either FOXJ3 or RGS1 ameliorated arthritis severity, improved pathological changes, and reduced osteoclastogenesis and bone erosion in vivo and in vitro. However, the effects of FOXJ3 silencing were negated by RGS1 overexpression. In conclusion, this study demonstrates that the RGS1 eRNA-driven transcriptional activation of the FOXJ3/RGS1 axis accelerates osteoclastogenesis through PLC-IP3R dependent Ca2+ response in RA. The finding may offer novel insights into the role of eRNA in gene transcription and osteoclastogenesis in RA.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"447-463"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431862","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}

引用次数: 0

Comparative Proteomics Analysis Reveals Distinct Molecular Phenotype and Biomarkers in Patients with Erythrodermic Atopic Dermatitis and Erythrodermic Psoriasis. 蛋白质组学对比分析揭示红皮病型特应性皮炎和红皮病型银屑病患者不同的分子表型和生物标记物

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-01 Epub Date: 2024-06-14 DOI: 10.1007/s10753-024-02078-3

Biao Song, Xin Ning, Lan Guo, Weida Liu, Hongzhong Jin

{"title":"Comparative Proteomics Analysis Reveals Distinct Molecular Phenotype and Biomarkers in Patients with Erythrodermic Atopic Dermatitis and Erythrodermic Psoriasis.","authors":"Biao Song, Xin Ning, Lan Guo, Weida Liu, Hongzhong Jin","doi":"10.1007/s10753-024-02078-3","DOIUrl":"10.1007/s10753-024-02078-3","url":null,"abstract":"Erythrodermic atopic dermatitis (EAD) and erythrodermic psoriasis (EP) are rare yet debilitating inflammatory skin disorders that propose challenges in diagnosis and discovering effective therapeutic targets. Despite their clinical and histological similarities, the underlying molecular mechanisms and systemic biomarkers of these diseases are substantially unclear. In this study, we sought to investigate the differential serum proteome of EP and EAD patients and identify biomarkers for these two subtypes of erythroderma. We recruited 14 EAD patients, 14 EP patients and 14 healthy controls. Serum samples were collected and analyzed using the Olink high-throughput platform to assess the levels of 269 inflammation-/immune response-/cardiovascular-related biomarkers. Both EAD and EP patients exhibited enhanced immune activation and dysregulated cardiovascular profiles compared to healthy controls. EAD demonstrated a more pronounced inflammation tone, characterized by Th1/Th2/Th22/IL-1-dominant patterns, as well as increased TNF superfamily, Th17, and apoptosis markers. Conversely, EP displayed inflammation with Th1/Th17/TNF-skewing and mild Th2 upregulation, along with notable increases in epidermal-development markers. Disease severity in EAD was strongly correlated with apoptosis/Th2 markers, while correlated with Th17 markers in EP. Furthermore, a panel of eight markers (IL-17A/IL-17C/PI3/CCL20/SH2D1A/SIRT2/DFFA/IL-13) was identified that effectively discriminated between EP and EAD, with an Area Under the Curve greater than 0.8. Our study comprehensively characterizes the circulating molecular profiles in EAD and EP patients, providing insights into the similarities and complexities of their inflammation phenotypes. The identified serum biomarkers have the potential to differentiate between EP and EAD, which could aid in the diagnosis and guiding tailored therapeutics.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"331-345"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320782","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}

引用次数: 0

Aspalathin, a Primary Rooibos Flavonoid, Alleviates Mast Cell-Mediated Allergic Inflammation by the Inhibition of FcεRI Signaling Pathway. 一种初级路依保斯黄酮类化合物 Aspalathin 通过抑制 FcεRI 信号通路缓解肥大细胞介导的过敏性炎症

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-01 Epub Date: 2024-05-23 DOI: 10.1007/s10753-024-02034-1

Yeyoung Kim, Soyoung Lee, Meiling Jin, Young-Ae Choi, Jin Kyeong Choi, Taeg Kyu Kwon, Dongwoo Khang, Sang-Hyun Kim

{"title":"Aspalathin, a Primary Rooibos Flavonoid, Alleviates Mast Cell-Mediated Allergic Inflammation by the Inhibition of FcεRI Signaling Pathway.","authors":"Yeyoung Kim, Soyoung Lee, Meiling Jin, Young-Ae Choi, Jin Kyeong Choi, Taeg Kyu Kwon, Dongwoo Khang, Sang-Hyun Kim","doi":"10.1007/s10753-024-02034-1","DOIUrl":"10.1007/s10753-024-02034-1","url":null,"abstract":"Mast cells are primary cells initiating allergic inflammation by the release of various allergic mediators, such as histamine and pro-inflammatory cytokines. Aspalathin (ASP) is the predominant flavonoid found exclusively in rooibos, an herb that has been traditionally used in allergy relief therapy. In the present study, we investigated the beneficial effects of ASP on mast cell-mediated allergic inflammation. For in vivo study, two well-known mast cell-mediated local and systemic allergic inflammation mouse models were used: passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis mouse models (ASA). Oral administration of ASP dose-dependently suppressed immunoglobulin (Ig)E-mediated PCA responses evidenced by Evans blue extravasation, ear thickening, and mast cell degranulation. ASP also significantly mitigated ovalbumin-induced ASA responses, including hypothermia, histamine secretion, and the production of IgE and interleukin-4. Notably, ASP was more effective in suppressing allergic inflammation than nothofagin, another prominent flavonoid known as an anti-allergic component of rooibos. The regulatory mechanism of mast cell activation by ASP was clarified using mast cell line and primary cultured mast cells (RBL-2H3 and mouse bone marrow-derived mast cells). ASP reduced IgE-stimulated mast cells degranulation and intracellular calcium influx by the inhibition of FcεRI signaling pathway (Lyn, Fyn, and Syk). Moreover, ASP reduced pro-inflammatory cytokine expressions by inhibiting two major transcription factors, nuclear factor of activated T cells and nuclear factor-κB. Collectively, we proposed that ASP could be a potential therapeutic candidate for the treatment of mast cell-mediated allergic inflammatory diseases.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"199-211"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079653","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}

引用次数: 0

Myeloid Cell mPGES-1 Deletion Attenuates Calcium Phosphate-induced Abdominal Aortic Aneurysm in Male Mice. 髓系细胞 mPGES-1 缺失可减轻磷酸钙诱发的雄性小鼠腹主动脉瘤

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-01 Epub Date: 2024-06-12 DOI: 10.1007/s10753-024-02055-w

Meina Guo, Shuang Ji, Hui Wang, Jiayang Zhang, Jingwen Zhu, Guangrui Yang, Lihong Chen

{"title":"Myeloid Cell mPGES-1 Deletion Attenuates Calcium Phosphate-induced Abdominal Aortic Aneurysm in Male Mice.","authors":"Meina Guo, Shuang Ji, Hui Wang, Jiayang Zhang, Jingwen Zhu, Guangrui Yang, Lihong Chen","doi":"10.1007/s10753-024-02055-w","DOIUrl":"10.1007/s10753-024-02055-w","url":null,"abstract":"Microsomal PGE2 synthase (mPGES)-1 is the key enzyme responsible for synthesizing inflammatory prostaglandin E2 (PGE2). Our previous studies have shown that deletion mPGES-1 in myeloid cells hinders atherogenesis, suppresses vascular proliferative response to injury and enhances survival after myocardial infarction. Here we aimed to further explore the influence of myeloid cell mPGES-1 deletion in abdominal aortic aneurysm (AAA) formation. The AAA was triggered by applying 0.5 M calcium phosphate (CaPO4) to the infrarenal aorta of both myeloid mPGES-1 knockout (Mac-mPGES-1-KO) and their littermate control Mac-mPGES-1-WT mice. AAA induction was assessed by calculating the expansion of the infrarenal aortic diameter 4 weeks after CaPO4 application. The maximum diameters of the aortas were measured by morphometry and the mean maximal diameters were calculated. Paraffin sections of the infrarenal aortas were examined for morphological analysis and immunohistochemical staining. The results showed that myeloid cell mPGES-1 deletion significantly mitigated AAA formation, including reducing expansion of the infrarenal aorta, preventing elastic lamellar degradation, and decreasing aortic calcium deposition. Immunohistochemical staining further indicated that macrophage infiltration and matrix metalloproteinase 2 (MMP2) expression was attenuated in the Mac-mPGES-1-KO aortas. Consistently, in vitro experiments showed that expression of pro-inflammatory cytokines and MMPs was significantly reduced when mPGES-1 was lacking in the primary cultured peritoneal macrophages. These data altogether demonstrated that deletion of mPGES-1 in myeloid cells may attenuate AAA formation and targeting myeloid cell mPGES-1 could potentially offer an effective strategy for the treatment and prevention of vascular inflammatory diseases.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"288-298"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305859","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}

引用次数: 0