Ping Li, Tao Li, Jinfeng Luo, Peng Yu, Tao Jiang, Xiangmin Zhou, Liang Yu, Aiping Chen, Yuzhu Wan, Li Shi
{"title":"IL-13 May Could Enhance the Proliferation and Affect the Differentiation of Nasal Epithelium Basal Cells Through the mTOR/p70S6K1 Pathway in Chronic Rhinosinusitis With Nasal Polyps.","authors":"Ping Li, Tao Li, Jinfeng Luo, Peng Yu, Tao Jiang, Xiangmin Zhou, Liang Yu, Aiping Chen, Yuzhu Wan, Li Shi","doi":"10.1155/mi/8108993","DOIUrl":"https://doi.org/10.1155/mi/8108993","url":null,"abstract":"<p><p><b>Background:</b> One of the hallmarks of Chronic rhinosinusitis with nasal polyps (CRSwNP) is the overexpression of IL-13, which may influence the proliferation and differentiation of nasal epithelial basal cells. However, the pathway is not clear enough, and the mTOR/p70S6K1 pathway is related to cell growth. This study was trying to explore if IL-13 could impact nasal epithelial basal cells through the mTOR/p70S6K1 pathway. <b>Methods:</b> PCR, western blot (WB), and immunohistochemistry (IHC) were used to compare the difference between IL-13 and the mTOR/p70S6K1 pathway-related molecules expression level between the healthy control (HC) and CRSwNP groups. WB, 5-ethynyl-2'-deoxyuridine staining, and Immunofluorescent (IF) were performed on human nasal epithelial progenitor cells (HNEPCs) to detect the proliferation ability under the effect of IL-13. In addition, qRT-PCR, WB, and IF were used to detect the differentiation ability with the stimulation of IL-13 in the air-liquid interface (ALI) system. <b>Results:</b> The expression of IL-13, mTOR/p70S6K1-related molecules, and proliferation-related molecules Ki67, CDK2, and cyclin E1 were upregulated in CRSwNP compared to HC. In HNEPCs, IL-13 could stimulate nasal epithelial cells proliferating through the mTOR/p70S6K1 pathway, and this phenomenon could be inhibited when mTOR (with rapamycin) and S6K1 (with PF-4708671) were blocked. In the ALI system, the effect of IL-13 added in the proliferation phase could persist in the proliferation and differentiation stage, affecting the nasal epithelial progenitor/stem cells' irregular differentiation. <b>Conclusion:</b> IL-13 may affect the proliferation and differentiation of nasal epithelial progenitor/stem cells through the mTOR/p70S6K1 pathway, which may affect the development of nasal polyps.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8108993"},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174091","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}
Hong Wei, Dongni Xia, Li Li, Linpan Liang, Lijun Ning, Cuiliu Gan, Ying Wu
{"title":"Baicalin Modulates Glycolysis <i>via</i> the PKC/Raf/MEK/ERK and PI3K/AKT Signaling Pathways to Attenuate IFN-I-Induced Neutrophil NETosis.","authors":"Hong Wei, Dongni Xia, Li Li, Linpan Liang, Lijun Ning, Cuiliu Gan, Ying Wu","doi":"10.1155/mi/8822728","DOIUrl":"10.1155/mi/8822728","url":null,"abstract":"<p><p>Type I interferon (IFN-I), a pivotal component of the host's innate antiviral immune system, can induce the formation of neutrophil extracellular traps (NETs) and facilitate inflammatory responses. Baicalin exhibits a range of pharmacological activities, including anti-inflammatory and immunomodulatory effects. It has been reported that neutrophil glycolysis plays a pivotal role in the formation of NETs and the regulation of inflammatory response in immune modulation, regulated by IFN-I. However, it remains unclear whether baicalin regulates IFN-I-induced NETs formation through glycolysis. In this study, we induced the formation of NETs <i>in vitro</i> using IFN-I and observed that baicalin significantly reduced the formation of IFN-I-induced NETs. Furthermore, baicalin inhibited the production of pro-inflammatory cytokines, specifically interleukin-1 beta (IL-1<i>β</i>) and interleukin-6 (IL-6), as well as the generation of reactive oxygen species (ROS) and chemotactic responses. Our findings further indicated that baicalin could inhibit both lactic acid and ATP levels in IFN-I-induced neutrophils, as well as the expression of glycolytic-related proteins, including HK2, HK3, PKM2, and LDHA. Moreover, following the administration of glycolytic agonists insulin, it was observed that heightened glycolytic activity significantly augmented NETs formation and the release of inflammatory cytokines, potentially regulated by PKC/Raf/MEK/ERK and PI3K/AKT signaling pathways. In conclusion, our findings indicated that baicalin may exert inhibitory effects on IFN-I-induced NETs formation and inflammatory cytokine production by modulating glycolysis, thereby providing further evidence for the potential clinical application of baicalin in the treatment of IFN-I-related inflammatory diseases.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8822728"},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150862","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}
Xiao-Yu Song, Ya-Kui Mou, Han-Rui Wang, Yao Wang, Wan-Chen Liu, Ting Yang, Cai-Yu Sun, Chao Ren, Xi-Cheng Song
{"title":"IL-6 and Olfactory Dysfunction: Focus on Changes, Effects, and Mechanisms.","authors":"Xiao-Yu Song, Ya-Kui Mou, Han-Rui Wang, Yao Wang, Wan-Chen Liu, Ting Yang, Cai-Yu Sun, Chao Ren, Xi-Cheng Song","doi":"10.1155/mi/5891188","DOIUrl":"10.1155/mi/5891188","url":null,"abstract":"<p><p>The sense of smell is vital for human life and risk identification. Many diseases can cause olfactory disorders, and early identification and intervention of olfactory disorders are crucial. Currently, the diagnosis of olfactory disorders in clinical practice mostly relies on subjective visual analog scale (VAS) evaluations, expensive and complex imaging, and neurophysiological examinations, which lead to poor patient compliance and low completion rates. Therefore, there is an urgent need to identify novel, objective, easily detectable biological indicators. Interleukin-6 (IL-6) is an inflammatory factor that is closely associated with olfactory dysfunction in various diseases. However, the role of IL-6 in the occurrence and development of olfactory disorders is not yet clear, which limits its clinical application. This article reviews the changes and possible mechanisms of IL-6 in various diseases associated with olfactory disorders, with the aim of providing a reference for the clinical application of IL-6 as a biomarker for olfactory disorders and promoting an in-depth exploration of its mechanism in the occurrence and development of olfactory disorders.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5891188"},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150868","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}
Agnes Schröder, Hanna Engelhardt, Andressa Nogueira, Björn Clausen, Christian Kirschneck, Jonathan Jantsch, Peter Proff, Kathrin Renner, Eva Paddenberg-Schubert
{"title":"The Mechanosensitive PIEZO1 Channel Contributes to the Reaction of RAW264.7 Macrophages to Mechanical Strain.","authors":"Agnes Schröder, Hanna Engelhardt, Andressa Nogueira, Björn Clausen, Christian Kirschneck, Jonathan Jantsch, Peter Proff, Kathrin Renner, Eva Paddenberg-Schubert","doi":"10.1155/mi/9998838","DOIUrl":"10.1155/mi/9998838","url":null,"abstract":"<p><p>The mechanosensitive channel 'piezo type mechanosensitive ion channel component 1' (PIEZO1) plays a regulatory role in the response of periodontal ligament fibroblasts (PDLFs) to the mechanical strain that occurs during orthodontic tooth movement. In addition to PDLFs, immune cells such as macrophages are also exposed to mechanical stimuli. Macrophages respond to mechanical strain with increased expression of inflammatory mediators. The role of PIEZO1 in this response remains elusive. To investigate the effect of PIEZO1 activation, RAW264.7 macrophages were stimulated with the PIEZO1 activator YODA1 without concurrent application of pressure. To further examine the specific role of PIEZO1 during mechanical strain, RAW264.7 macrophages were exposed to mechanical strain without and with simultaneous inhibition of PIEZO1 either by chemical inhibition (GsMTx4) or siRNA silencing. The expression of genes and proteins involved in orthodontic tooth movement was examined by quantitative PCR, western blot, and enzyme-linked immunosorbent assay (ELISA). Activation of PIEZO1 by YODA1 or mechanical strain increased the expression of inflammatory cytokines and osteoprotegerin (Opg), which is critically involved in bone remodeling processes. Conversely, inhibition of the PIEZO1 channel attenuates the effects of mechanical stress. In conclusion, our data demonstrate that the PIEZO1 channel is a major contributor to the response of macrophages to mechanical strain encountered during orthodontic tooth movement and affects the expression of inflammatory and bone remodeling factors.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9998838"},"PeriodicalIF":4.4,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150903","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":"Detection of the Prognostic Gene CYB5D2 in Cervical Squamous Epithelial Lesions.","authors":"Yanan Liu, Guoqiang Zhao, Yanqing Kong, Fengyuan Zhou, Tong Zhang, Xiaohang Chen, Haiyan Hu, Fengxiang Wei","doi":"10.1155/mi/2360364","DOIUrl":"10.1155/mi/2360364","url":null,"abstract":"<p><p>CYB5D2 is a novel tumor suppressor gene that exhibits ectopic expression in various tumors. This study explored its significance in cervical cancer screening and prognosis by examining its expression in cervical precancerous lesions and cancer tissues and analyzing follow-up data. CYB5D2 expression was comprehensively assessed in 112 clinical samples, combined with routine cervical cancer screening methods to evaluate its early detection potential. Postoperative survival data from cervical cancer patients were analyzed using Kaplan-Meier curves to examine the association between CYB5D2 protein expression and clinicopathological characteristics, as well as its prognostic implications. Results revealed a progressive downregulation of CYB5D2 expression with advancing cervical lesions. Immunohistochemical detection of CYB5D2 protein outperformed ThinPrep cytology test (TCT), DNA aneuploidy analysis, and HR-HPV E6/E7 mRNA testing (mRNA expression of the E6 and E7 genes in high-risk HPV virus) in diagnosing high-grade squamous intraepithelial lesions (HSIL+) of the cervix. Combined testing of TCT, HR-HPV E6/E7 mRNA, and CYB5D2 achieved 100% sensitivity and negative predictive value for HSIL+. In conclusion, low CYB5D2 expression was identified as an independent risk factor for progression-free survival (PFS) in cervical cancer patients. Incorporating CYB5D2 testing into routine screening protocols for squamous cell lesions, along with TCT and HPV testing, may enhance diagnostic efficiency and provide prognostic value for adverse outcomes.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"2360364"},"PeriodicalIF":4.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110912","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}
Amirhossein Heidari, Amirhossein Shahbazi Mazid, Mohammad Behroozfar, Negar Ghotbi, Fatemeh Fathabadi, Sara Eghbali, Nazila Heidari
{"title":"Efficacy and Safety of Syk and BTK Inhibitors in Immune Thrombocytopenia: A Comprehensive Review of Emerging Evidence.","authors":"Amirhossein Heidari, Amirhossein Shahbazi Mazid, Mohammad Behroozfar, Negar Ghotbi, Fatemeh Fathabadi, Sara Eghbali, Nazila Heidari","doi":"10.1155/mi/5578929","DOIUrl":"10.1155/mi/5578929","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a reduced platelet count, resulting in bleeding risks and compromised quality of life. Advances in understanding ITP pathogenesis have revealed critical roles for spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) in Fc receptor (FcR)-mediated immune pathways, which are central to autoantibody production and platelet destruction. We sought to evaluate the efficacy and safety of Syk and BTK inhibitors in the management of ITP. PubMed/Medline, Scopus, and Web of Science databases were systematically searched up to July 28, 2024. Clinical studies with available full-text in English were included. Fostamatinib, an FDA-approved Syk inhibitor, has shown efficacy in enhancing platelet counts and reducing bleeding events in refractory ITP patients. Among the newer Syk inhibitors, sovleplenib demonstrated rapid and sustained platelet increases in clinical trials, with an 80% response rate at the 300 mg dosage and a favorable safety profile. Additionally, BTK inhibitors, including rilzabrutinib and orelabrutinib, have shown potential in clinical trials, offering increased platelet stability and favorable safety profiles in ITP cases. Syk and BTK inhibitors hold potential as targeted therapies for refractory ITP, with evidence supporting their ability to improve clinical outcomes and enhance patient quality of life. Continued research is warranted to optimize these therapies and confirm their long-term efficacy and safety in diverse patient populations.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5578929"},"PeriodicalIF":4.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094160","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}
Jiayuan Song, Ziyi Xu, Han Yu, Aimin Li, Yiying Liu, Meiying Jin
{"title":"Association of Three Composite Inflammatory and Lipid Metabolism Indicators With Cardiovascular-Kidney-Metabolic Syndrome: A Cross-Sectional Study Based on NHANES 1999-2020.","authors":"Jiayuan Song, Ziyi Xu, Han Yu, Aimin Li, Yiying Liu, Meiying Jin","doi":"10.1155/mi/6691516","DOIUrl":"https://doi.org/10.1155/mi/6691516","url":null,"abstract":"<p><p><b>Background:</b> Various leukocyte-to-high-density lipoprotein cholesterol (HDL-C) ratios, namely the neutrophil to HDL-C ratio (NHR), lymphocyte to HDL-C ratio (LHR), and monocyte to HDL-C ratio (MHR), have been identified as potential inflammatory biomarkers. Despite this, the intricate relationship between these ratios and Cardiovascular-Kidney-Metabolic (CKM) Syndrome has yet to be fully elucidated. This study aims to explore the associations between these white blood cell ratios and the presence of CKM Syndrome. <b>Methods:</b> This cross-sectional retrospective analysis utilized data from 19,534 individuals diagnosed with CKM Syndrome, sourced from the National Health and Nutrition Examination Survey (NHANES) database covering the years 1999-2020. Participants were stratified, and relevant covariates were adjusted during the analysis. Weighted logistic regression models were employed to statistically assess the relationships between the inflammatory markers and the differing stages of CKM Syndrome, with stage 0 serving as the reference point. <b>Results:</b> After adjusting for all the covariates, high levels of three inflammatory indicators were associated with higher odds of having CKM Syndrome stage 1-4, using stage 0 as a reference. When we assessed the associations between inflammatory indicators with stage 3-4 with stage 0-1-2 as the reference group, we found that inflammatory indicators still increased the risk of higher CKM Syndrome stage. The dose-response relationship revealed that the inflammatory indicators increased the risk of higher CKM Syndrome stage. After conducting subgroup analyses, we found that LHR and education, as well as LHR, MHR, and drinking status, had significant interactions. <b>Conclusion:</b> Elevated NHR, LHR, and MHR are significantly associated with an increased risk of CKM Syndrome across stages 1-4.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6691516"},"PeriodicalIF":4.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078994","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":"Cross Talk Between Macrophages and Podocytes in Diabetic Nephropathy: Potential Mechanisms and Novel Therapeutics.","authors":"Siming Yu, Zehui Han, Chunsheng Li, Xinxin Lu, Yue Li, Xingxing Yuan, Dandan Guo","doi":"10.1155/mi/8140479","DOIUrl":"https://doi.org/10.1155/mi/8140479","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a leading cause of chronic kidney disease and end-stage renal failure worldwide. Podocytes, essential components of the glomerular filtration barrier (GFB), are profoundly affected in the diabetic milieu, resulting in structural and functional alterations. Concurrently, macrophages, pivotal innate immune cells, infiltrate the diabetic kidney and exhibit diverse activation states influenced by the local environment, playing a crucial role in kidney physiology and pathology. This review synthesizes current insights into how the dynamic cross talk between these two cell types contributes to the progression of DN, exploring the molecular and cellular mechanisms underlying this interaction, with a particular focus on how macrophages influence podocyte survival through various forms of cell death, including apoptosis, pyroptosis, and autophagy. The review also discusses the potential of targeting macrophages to develop more effective treatments for DN.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8140479"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971390","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":"<i>Pogostemon cablin</i> Acts as a Key Regulator of NF-<i>κ</i>B Signaling and Has a Potent Therapeutic Effect on Intestinal Mucosal Inflammation.","authors":"Yuqing Deng, Xin Liang, Long Zhao, Xin Zhou, Jianqin Liu, Zhi Li, Shanshan Chen, Guohui Xiao","doi":"10.1155/mi/9000672","DOIUrl":"https://doi.org/10.1155/mi/9000672","url":null,"abstract":"<p><p>Persistent intestinal inflammation is a major contributor to various diseases, including digestive disorders, immune dysregulation, and cancer. The NF-<i>κ</i>B signaling pathway is pivotal in the inflammatory response of intestinal cells, regulating the secretion of inflammatory factors, mediating signal transduction, and activating receptors. In colitis, NF-<i>κ</i>B signaling and its effector molecules are excessively activated by various stimuli, leading to overexpression of inflammatory mediators and immune regulators. Colitis, an inflammation of the intestinal mucosa, underlies many intestinal diseases, with increasing incidence. Traditional treatments such as glucocorticoids and nonsteroidal antiinflammatory drugs have significant limitations and side effects. <i>Pogostemon cablin</i>, a traditional Chinese medicine and food, is widely used in food, spices, and pharmaceuticals. Studies have demonstrated its positive therapeutic effects on intestinal inflammation, primarily through regulation of the NF-<i>κ</i>B signaling pathway. Moreover, <i>P. cablin</i> and its active components exhibit pharmacological activities such as antiapoptotic, antioxidant, and antitumor effects. This review summarizes the original research on treating intestinal mucosal inflammation via NF-<i>κ</i>B signaling regulation using <i>P. cablin</i> and its active components, providing new insights for colitis treatment.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9000672"},"PeriodicalIF":4.4,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034361","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":"Liangxue Qushi Zhiyang Decoction Inhibits Atopic Dermatitis in Mice via Fc<i>γ</i>R-Mediated Phagocytosis.","authors":"Lili Zhang, Linxian Li, Zhanxue Sun","doi":"10.1155/mi/7068964","DOIUrl":"https://doi.org/10.1155/mi/7068964","url":null,"abstract":"<p><p><b>Background:</b> Liangxue Qushi Zhiyang Decoction (LQZ) is a traditional formula known for its efficacy in treating Atopic Dermatitis (AD). However, the specific mechanisms through which LQZ alleviates AD symptoms remain largely unknown. The objective of this study is to investigate the protective effects of LQZ on AD and to uncover its potential mechanisms of action. <b>Methods:</b> An AD model was established in mice using 2,4-dinitrochlorobenzene (DNCB). Mice were then orally administered LQZ or prednisolone (PDN). Throughout the treatment period, dermatitis scores and scratching frequencies of the mice were regularly monitored. Histopathological analyses were conducted using hematoxylin and eosin (H&E) staining and toluidine blue (TB) staining. Serum levels of inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Further, tandem mass tag (TMT) labeling quantitative proteomics was employed to identify differentially expressed proteins (DEPs). Enrichment analysis was conducted to pinpoint potential targets and pathways involved in LQZ's therapeutic action. Finally, validation experiments were performed to further explore the specific pathways and core targets of LQZ in AD treatment.. <b>Results:</b> LQZ treatment notably mitigated the skin barrier damage and inflammatory response induced by DNCB in AD mice, and reduced the serum levels of IgE, IL-4, and IL-1<i>β</i>. Proteomic analysis identified 248 proteins with differential expression, implicating multiple pathways in LQZ' therapeutic action. Among these, the Fc gamma R(Fc<i>γ</i>R)-mediated phagocytosis pathway emerged as a crucial factor in AD's inflammatory and immune responses. Key proteins associated with this pathway, including Fc-gamma RIII (Fcgr3), V-yes-1 Yamaguchi sarcoma viral related oncogene homolog (Lyn), Tyrosine-protein kinase (Syk), Phosphoinositide phospholipase C-gamma-2 (Plcg2), Neutrophil cytosol factor 1 (Ncf1), Ras-related C3 botulinum toxin substrate 2 (Rac2) and Actin-related protein 2/3 complex subunit 3 (Arpc3), exhibited significantly reduced expression levels following LQZ treatment. <b>Conclusion:</b> LQZ is effective in treating AD by alleviating skin barrier damage and inflammatory reactions. Its anti-AD properties of LQZ may be attributed to the inhibition of the Fc<i>γ</i>R-mediated phagocytic pathway.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7068964"},"PeriodicalIF":4.4,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032021","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}