Cytokine最新文献

{"title":"Optimizing CAR-T cell Culture: Differential effects of IL-2, IL-12, and IL-21 on CAR-T cells","authors":"Mengmeng Zhang ,&nbsp;JingJing Kong ,&nbsp;Fanxiang Yin ,&nbsp;Jianxiang Shi ,&nbsp;Jin Li ,&nbsp;Zan Qiu ,&nbsp;Baohong Yue ,&nbsp;Shuya Wang ,&nbsp;Nannan Sun ,&nbsp;Quande Lin ,&nbsp;Liyan Fu ,&nbsp;Xiaoqian Wang ,&nbsp;Xianlei Sun ,&nbsp;Yanxia Gao ,&nbsp;Yong Jiang ,&nbsp;Rongqun Guo","doi":"10.1016/j.cyto.2024.156758","DOIUrl":"10.1016/j.cyto.2024.156758","url":null,"abstract":"<div><h3>Background</h3><p>Chimeric antigen receptor (CAR)-T therapy has demonstrated sustained clinical remission in numerous hematologic malignancies and has expanded to encompass solid tumors and autoimmune diseases. While progress is being made in establishing optimal culture conditions for CAR-T cells, the identification of the most effective cytokine for promoting their persistence in vitro remains elusive.</p></div><div><h3>Methods</h3><p>Here, we employed scRNA-seq (single-cell RNA sequencing) analysis to investigate the potential alterations in biological processes within CAR-T cells following exposure to cytokines (IL-2, IL-12, and IL-21) and antigens. Transcriptomic changes in diverse CAR-T groups were compared following various treatments, with a focus on epigenetic modifications, metabolic shifts, cellular senescence, and exhaustion.</p></div><div><h3>Results</h3><p>Our study reveals that CAR-T cells treated with antigen, IL-2, and IL-12 exhibit signs of exhaustion and senescence, whereas those treated with IL-21 do not display these characteristics. The activities of glycolysis and epigenetic changes were significantly increased by treatments with antigens, IL-2, and IL-12, while IL-21 treatment maintained the oxidative phosphorylation (OXPHOS) of CAR-T cells.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that IL-21 may play a role in preventing senescence and could be utilized in combination with other strategies, such as IL-2 and IL-12, for CAR-T culture.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156758"},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lupeol stimulates iNOS, TNF-α, and IL-10 expression in the U937 cell line infected with old-world Leishmania donovani","authors":"Talib Fadhil Abbas ,&nbsp;Hayder Z. Ali","doi":"10.1016/j.cyto.2024.156757","DOIUrl":"10.1016/j.cyto.2024.156757","url":null,"abstract":"<div><h3>Objective</h3><p>Visceral leishmaniasis is a neglected tropical disease that can be lethal if not treated. The available medicines have severe side effects, such as toxicity and drug resistance. Various investigations are looking into new anti-leishmanial compounds from natural products that have little impact on host cells. Lupeol, a triterpenoid present in the flora of many edible plants, has been shown to have antimicrobial properties. The present study investigated the immunomodulatory effects of lupeol on U937 macrophages infected with <em>Leishmania donovani</em>, focusing on the expression of key cytokines and enzymes involved in the immune response.</p></div><div><h3>Methods</h3><p>U937 macrophages were infected with <em>Leishmania donovani</em> amastigotes and treated with varying concentrations of lupeol throughout three days. The expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) were measured using real-time polymerase chain reaction (RT-PCR). A positive simulation of gene expression was estimated using ΔΔCT to assess relative expression.</p></div><div><h3>Results</h3><p>The results demonstrated that lupeol significantly upregulated iNOS and TNF-α expression, especially at higher concentrations, indicating enhanced pro-inflammatory and anti-leishmanial activity. Interestingly, IL-10 expression also increased, suggesting a complex immunomodulatory role of lupeol that involves both pro-inflammatory and anti-inflammatory pathways. Pearson correlation analysis revealed a strong association between iNOS and TNF-α (0.97692), as well as a moderate correlation between iNOS and IL-10 (0.51603).</p></div><div><h3>Conclusion</h3><p>These findings suggest that lupeol may promote a balanced immune response, enhancing the body’s ability to combat <em>L. donovani</em> while potentially mitigating excessive inflammation. Lupeol can potentially serve as a novel therapeutic agent against visceral leishmaniasis.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156757"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID 19: Prevention and treatment through the Indian perspective","authors":"Harish Chandra ,&nbsp;Archana Yadav ,&nbsp;Rajendra Prasad ,&nbsp;Kalpana Sagar ,&nbsp;Nitin Bhardwaj ,&nbsp;Kartikey Kumar Gupta ,&nbsp;Ghanshyam Singh Thakur ,&nbsp;Manisha Nigam ,&nbsp;Raffaele Pezzani ,&nbsp;João Paulo Martins de Lima ,&nbsp;Henrique Douglas Melo Coutinho ,&nbsp;Abhay Prakash Mishra","doi":"10.1016/j.cyto.2024.156756","DOIUrl":"10.1016/j.cyto.2024.156756","url":null,"abstract":"<div><p>The most destructive period the world has experienced seems to be behind us. Not a single nation was spared by this disease, and many continue to struggle today. Even after recovering from COVID, patient may continue to experience some post-COVID effects, such as heart irregularities or a decline in lung vitality. In the past three years (2019–2022), the world has witnessed the power of a small entity, a single peculiar virus. Science initially appeared to be helpless in this regard, but due to the emergence of disease, pharmaceutics (the development of anti-covid drugs), immunology (the rapid antigen test), microbiology (the isolation of viruses from infected people), biotechnology (the development of recombinant vaccines), biochemistry (the blood profile, the D-dimer test), and biochemistry (blood profile, D-dimer test), biophysics (PCR, RT-PCR, CT Scan, MRI) had worked together to fight the disease. The results of these efforts are the development of new diagnostic techniques, possible treatment and finally the availability of vaccines against COVID-19. However, it is not proven that the treatment through the traditional medical system is directly active on SARS-CoV-2 but is instead indirectly acting on SARS-CoV-2 effects by improving symptoms derived from the viral disease. In India, the traditional system of medicine and tradition knowledge together worked in the pandemic and proved effective strategies in prevention and treatment of SARS-CoV-2. The use of effective masks, PPE kits, plasma therapy, yoga, lockdowns and social seclusion, use of modern antiviral drugs, monoclonal antibodies, herbal remedies, homoeopathy, hygienic practice, as well as the willpower of people, are all contributing to the fight against COVID. Which methods or practices will be effective against COVID nobody is aware since medical professionals who wear PPE kits do not live longer, and some people in India who remained unprotected and roamed freely were not susceptible to infection. The focus of this review is on the mode of transmission, diagnosis, preventive measures, vaccines currently under development, modern medicine developed against SARS-CoV-2, ayurvedic medicine used during pandemic, homoeopathic medicine used during pandemic, and specific yoga poses that can be used to lessen COVID-related symptoms.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156756"},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UFMylation is involved in serum inflammatory cytokines generation and splenic T cell activation induced by lipopolysaccharide","authors":"Sixu Wang ,&nbsp;Yuyang Liu ,&nbsp;Ming Su ,&nbsp;Jing Yang ,&nbsp;Hui Liu ,&nbsp;Wei Qiu","doi":"10.1016/j.cyto.2024.156755","DOIUrl":"10.1016/j.cyto.2024.156755","url":null,"abstract":"<div><p>UFMylation, a novel ubiquitin-like protein modification system, has been recently found to be activated in inflammation. However, the effects of UFMylation activation on inflammation in vivo remains unclear. In the present study, we generated a UFMylation activated mice using transgenic (TG) techniques. Lipopolysaccharide (LPS) was used to induce systemic inflammation in both TG and non-transgenic (NTG) mice. Serum cytokines were detected using a Mouse Cytokine Array, and the proportions of splenic NK, B and T cells were determined by using flow cytometry. We found that TG mice showed increased serum G-CSF, TNF RII and decreased serum TCA-3, CD30L, bFGF, IL-15 and MIG compared with NTG mice at baseline. Furthermore, serum cytokines in TG mice exhibited different responses to LPS compared to NTG mice. LPS up-regulated serum TNF RII, G-CSF, MCP-5, RANTES, KC, BLC, MIG and down-regulated IL-1b, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-12p40, IL-15, IL-17, IFN-γ, TCA-3, Eotaxin-2, LIX, MCP-1, TNFα, GM-CSF in NTG mice, whereas LPS up-regulated G-CSF, MCP-5, RANTES, KC, BLC, MIG, ICAM-1, PF4, Eotaxin, CD30L, MIP-1a, TNFRI and down-regulated IL-1b, IL-3, LIX, MCP-1, TNFα, GM-CSF in TG mice. Data from flow cytometry indicated that LPS significantly reduced the percentages of NK and NKT cells in NTG mice, whereas UFMylation activation inhibited LPS-induced NKT cell decrease. The proportions of B cells, total CD4⁺ and total CD8⁺ T cells were comparable between TG and NTG mice in response to LPS treatment, whereas the percentages of CD4⁺CD69⁺ and CD8⁺CD69⁺T cells were lower in TG mice. These findings suggest that UFMylation may alter LPS-induced serum cytokine profile and participate in splenic T cell activation in vivo.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156755"},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Poly I:C vaccination drives transient CXCL9 expression near B cell follicles in the lymph node through type-I and type-II interferon signaling” [Cytokine 183 (2024) 156731]","authors":"Alexander G. Ball ,&nbsp;Katerina Morgaenko ,&nbsp;Parastoo Anbaei ,&nbsp;Sarah E. Ewald ,&nbsp;Rebecca R. Pompano","doi":"10.1016/j.cyto.2024.156752","DOIUrl":"10.1016/j.cyto.2024.156752","url":null,"abstract":"","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156752"},"PeriodicalIF":3.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043466624002564/pdfft?md5=c51f6da18faee37a82f4fa67087590ba&pid=1-s2.0-S1043466624002564-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195212","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":"Monkeypox (Mpox) vs. Innate immune responses: Insights into evasion mechanisms and potential therapeutic strategies","authors":"Pouya Pashazadeh Azari ,&nbsp;Mohammad Rezaei Zadeh Rukerd ,&nbsp;Javad Charostad ,&nbsp;Davood Bashash ,&nbsp;Niloofar Farsiu ,&nbsp;Saleh Behzadi ,&nbsp;Seyedeh Mahdieh Khoshnazar ,&nbsp;Sajjad Heydari ,&nbsp;Mohsen Nakhaie","doi":"10.1016/j.cyto.2024.156751","DOIUrl":"10.1016/j.cyto.2024.156751","url":null,"abstract":"<div><p>Orthopoxviruses, a group of zoonotic viral infections, have emerged as a significant health emergency and global concern, particularly exemplified by the re-emergence of monkeypox (Mpox). Effectively addressing these viral infections necessitates a comprehensive understanding of the intricate interplay between the viruses and the host’s immune response. In this review, we aim to elucidate the multifaceted aspects of innate immunity in the context of orthopoxviruses, with a specific focus on monkeypox virus (MPXV). We provide an in-depth analysis of the roles of key innate immune cells, including natural killer (NK) cells, dendritic cells (DCs), and granulocytes, in the host defense against MPXV. Furthermore, we explore the interferon (IFN) response, highlighting the involvement of toll-like receptors (TLRs) and cytosolic DNA/RNA sensors in detecting and responding to the viral presence. This review also examines the complement system’s contribution to the immune response and provides a detailed analysis of the immune evasion strategies employed by MPXV to evade host defenses. Additionally, we discuss current prevention and treatment strategies for Mpox, including pre-exposure (PrEP) and post-exposure (PoEP) prophylaxis, supportive treatments, antivirals, and vaccinia immune globulin (VIG).</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156751"},"PeriodicalIF":3.7,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142148467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The critical roles of IGFs in immune modulation and inflammation","authors":"Xin Wang ,&nbsp;Lijuan Cao ,&nbsp;Shisong Liu ,&nbsp;Yipeng Zhou ,&nbsp;Jiarui Zhou ,&nbsp;Wenxuan Zhao ,&nbsp;Shengqi Gao ,&nbsp;Rui Liu ,&nbsp;Yufang Shi ,&nbsp;Changshun Shao ,&nbsp;Jiankai Fang","doi":"10.1016/j.cyto.2024.156750","DOIUrl":"10.1016/j.cyto.2024.156750","url":null,"abstract":"<div><p>Insulin-like growth factors (IGFs) are crucial for embryonic and postnatal growth and development, influencing cell survival, metabolism, myogenesis, and cancer progression. Many studies have demonstrated that IGFs also play prominent roles in the modulation of both innate and adaptive immune systems during inflammation. Strikingly, IGFs dictate the phenotype and functional properties of macrophages and T cells. Furthermore, the interplay between IGFs and inflammatory cytokines may generate tissue-protective properties during inflammation. Herein, we review the recent advances on the dialogue between immune cells and IGFs, especially zooming in on the significance of immunomodulatory properties in inflammatory conditions, cancer and autoimmune diseases. The investigation of IGFs may have broad clinical implications.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156750"},"PeriodicalIF":3.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCL4/CCR5 regulates chondrocyte biology and OA progression","authors":"Hongjian Deng ,&nbsp;Pengfei Xue ,&nbsp;Xiaogang Zhou ,&nbsp;Yuntao Wang ,&nbsp;Wei Liu","doi":"10.1016/j.cyto.2024.156746","DOIUrl":"10.1016/j.cyto.2024.156746","url":null,"abstract":"<div><h3>Background</h3><p>Osteoarthritis (OA) is a common musculoskeletal disorder characterized by chondrocyte apoptosis and extracellular matrix degradation. This study aimed to investigate the role of CCL4/CCR5 in regulating chondrocyte apoptosis and reactive oxygen species (ROS) levels in OA progression.</p></div><div><h3>Methods</h3><p>Bioinformatics analysis was employed to identify CCL4 as the target gene, following which primary chondrocytes were treated with varying concentrations of CCL4. Apoptosis rate of chondrocytes and ROS levels were assessed using flow cytometry. The mechanism by which CCL4 regulated the extracellular matrix was investigated through Western blot and Immunofluorescence analyses. Additionally, maraviroc, a CCR5 inhibitor, was administered to chondrocytes in order to explore the potential signaling pathway of CCL4/CCR5.</p></div><div><h3>Results</h3><p>Our study found that CCL4 was predominantly up-regulated among the top 10 hub genes identified in RNA-sequencing analysis. Validation through quantitative polymerase chain reaction (qPCR) confirmed elevated CCL4 expression in patients with Hip joint osteoarthritis, knee joint osteoarthritis, and facet joint osteoarthritis. The upregulation of CCL4 was associated with an increase in chondrocyte apoptosis and ROS levels. Mechanistically, CCL4, upon binding to its receptor CCR5, triggered the downstream phosphorylation of P65 in the nuclear factor-κB (NF-κB) signaling pathway. In vitro experiments demonstrated that treatment with maraviroc mitigated chondrocyte apoptosis, reduced intracellular ROS levels, and attenuated extracellular matrix degradation.</p></div><div><h3>Conclusion</h3><p>The study highlights the critical role of CCL4/CCR5 in modulating chondrocyte apoptosis and ROS levels in OA progression. Targeting this pathway may offer promising therapeutic interventions for mitigating the pathogenic mechanisms associated with OA.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156746"},"PeriodicalIF":3.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbe-associated molecular patterns derived from fungi and bacteria promote IgG4 antibody production in patients with type 1 autoimmune pancreatitis","authors":"Naoya Omaru ,&nbsp;Yasuo Otsuka ,&nbsp;Akane Hara ,&nbsp;Masayuki Kurimoto ,&nbsp;Natsuki Okai ,&nbsp;Yasuhiro Masuta ,&nbsp;Sho Masaki ,&nbsp;Ken Kamata ,&nbsp;Kosuke Minaga ,&nbsp;Hajime Honjo ,&nbsp;Yasuyuki Arai ,&nbsp;Kohei Yamashita ,&nbsp;Masatoshi Kudo ,&nbsp;Tomohiro Watanabe","doi":"10.1016/j.cyto.2024.156748","DOIUrl":"10.1016/j.cyto.2024.156748","url":null,"abstract":"<div><p>Enhanced IgG4 antibody (Ab) response is a prominent feature of type 1 autoimmune pancreatitis (AIP). Innate immune responses associated with IgG4 Ab production are poorly defined. We have previously reported that peripheral blood mononuclear cells (PBMCs) isolated from patients with type 1 AIP produce large amounts of IgG4 Abs upon stimulation with bacterial cell wall components. In addition, we showed that activation of plasmacytoid dendritic cells producing interferon (IFN)-α, interleukin (IL)-33, and B cell-activating factor (BAFF) upon sensing intestinal bacteria mediates the development of experimental AIP. In this study, we attempted to clarify the role of innate immunity against fungi in inducing enhanced IgG4 Ab responses in type 1 AIP. PBMCs isolated from healthy controls and patients with type 1 AIP were stimulated with a broad range of bacterial and fungal cell wall components. The concentrations of IgG1, IgG4, and cytokines were measured using enzyme-linked immunosorbent assays. Cell wall components derived from bacteria and fungi induced IgG1 and IgG4 Ab production in patients with type 1 AIP. Various types of microbe-associated molecular pattern motifs enhanced IgG4 Ab production in patients with type 1 AIP compared with the limited motifs in healthy controls. The enhanced IgG1 and IgG4 Ab production that followed in response to bacterial and fungal cell wall components was parallel to that of IFN-α, IFN-γ, IL-10, IL-33, and BAFF. In conclusion, cell wall components derived from fungi as well as bacteria promote IgG4 Ab responses in patients with type 1 AIP.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156748"},"PeriodicalIF":3.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apocynin alleviates thioacetamide-induced acute liver injury: Role of NOX1/NOX4/NF-κB/NLRP3 pathways","authors":"Dalia H. El-Kashef ,&nbsp;Noha Abdel-Rahman ,&nbsp;Maha H. Sharawy","doi":"10.1016/j.cyto.2024.156747","DOIUrl":"10.1016/j.cyto.2024.156747","url":null,"abstract":"<div><p>The liver has a distinctive capacity to regenerate, yet severe acute injury can be life-threatening if not treated appropriately. Inflammation and oxidative stress are central processes implicated in the pathophysiology of acute livery injury. NOX isoforms are important enzymes for ROS generation, NF-κB and NLRP3 activation, its inhibition could be vital in alleviating acute liver injury (ALI). Here in our study, we used apocynin, a natural occurring potent NOX inhibitor, to explore<!--> <!-->its potential protective effect against thioacetamide (TAA)-induced ALI through modulating crucial oxidative and inflammatory pathways. Rats were injected once with TAA (500 mg/kg/<em>i.p</em>) and treated with apocynin (10 mg/kg/<em>i.p</em>) twice before TAA challenge. Sera and hepatic tissues were collected for biochemical, mRNA expression, western blot analysis and histopathological assessments. Pretreatment with apocynin improved liver dysfunction evidenced by decreased levels of aminotransferases, ALP, GGT and bilirubin. Apocynin reduced mRNA expression of NOX1 and NOX4 which in turn alleviated oxidative stress, as shown by reduction in MDA and NOx levels, and elevation in GSH levels and<!--> <!-->catalase and SOD activities. Moreover, apocynin significantly reduced MPO gene expression. We also demonstrate that apocynin ameliorated inflammation through activating IκBα and suppressing IKKα, IKKβ, NF-κBp65 and p-NF-κBp65, IL-6 and<!--> <!-->TNF-α. Additionally, apocynin potentiated the gene expression of anti-inflammatory IL-10 and reduced levels of hepatic NLRP3, Caspase-1 and IL-1β. These results suggest that apocynin protects against ALI in association with the inhibition of NOX1 and NOX4 and regulating oxidative and inflammatory pathways.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156747"},"PeriodicalIF":3.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}