Cytokine最新文献

{"title":"Upregulating lncRNA GUSBP11 protects chondrocytes from IL-1β-induced inflammatory damage via inhibiting miR-122-5p","authors":"Zhanqiu Xu ,&nbsp;Peigang Guo ,&nbsp;Lujun Li ,&nbsp;Zhiyuan Li ,&nbsp;Hong Li","doi":"10.1016/j.cyto.2025.156858","DOIUrl":"10.1016/j.cyto.2025.156858","url":null,"abstract":"<div><div>Studies have demonstrated that several lncRNAs exhibit abnormal expression levels in patients suffering from osteoarthritis, and in-depth investigation of these aberrantly expressed lncRNAs may pave the way for innovative therapeutic strategies targeting OA. The aim of this study was to examine the expression of glucuronidase beta pseudogene 11 (GUSBP11) in OA patients and to elucidate its potential molecular mechanism. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect GUSBP11 levels on cartilage tissues and serum samples obtained from OA patients. To establish an in vitro OA cell model, interleukin-1β (IL-1β) was utilized to induce CHON-001 and ATDC5 cell lines. Cell counting kit-8 (CCK-8) assay and flow cytometry were performed to evaluate cell viability and apoptosis, and enzyme-linked immunosorbent assay (ELISA) was employed to qualify the levels of inflammatory factors. StarBase database predicted that miR-122-5p was the target gene of GUSBP11. Subsequently, luciferase reporter genes were conducted to validate this interaction. Potential target genes of miR-122-5p were predicted, followed by gene function annotation and correlation analysis of these targets. Our findings revealed that GUSBP11 expression was markedly decreased in both the cartilage tissues and serum of OA patients. Diminished levels of GUSBP11 showed high diagnostic accuracy for OA. In the IL-1β-induced OA cell model, GUSBP11 expression was notably reduced, leading to decreased cell viability, an increase in apoptotic cells, and elevated levels of inflammatory factors. Up-regulation of GUSBP11 significantly ameliorated these adverse effects. Luciferase reporter genes confirmed the interaction between GUSBP11 and miR-122-5p, indicating that an increase in miR-122-5p drastically inhibited cell viability while promoting apoptosis and inflammation. In conclusion, within the context of the in vitro OA cell model, GUSBP11 appears to exacerbate IL-1β-induced chondrocyte inflammation through the up-regulation of miR-122-5p. This underscores the potential of GUSBP11 as a novel target and avenue for therapeutic intervention in the treatment of OA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156858"},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997494","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":"Extracellular HSP70 facilitated β-glucan induced trained immunity in macrophages to suppress sepsis via TLR2-NF-κB axis","authors":"Ran Qi ,&nbsp;Xin Cheng ,&nbsp;Shan Chen ,&nbsp;Jinjun Fan","doi":"10.1016/j.cyto.2025.156861","DOIUrl":"10.1016/j.cyto.2025.156861","url":null,"abstract":"<div><div>Sepsis is a common systemic infectious disease followed by extremely high incidence and mortality with no effective treatment and clinical drugs. As a key mediator involved in infection and immunity, it has been reported that sepsis patients are accompanied by increased heat shock protein 70 (HSP70). Trained immunity is a novel innate immunity approach that can be activated by β-glucan to fight against sepsis. The mechanism of HSP70 activating trained macrophages against sepsis needs further elucidation. Trained immunity and sepsis models were established by β-glucan and LPS individually both in vivo and in vitro. We demonstrated that HSP70 was significantly upregulated in septic mice serum, and HSP70 could protect mice from sepsis by activating β-glucan-trained macrophages as an ideal secondary inducer via TLR2-NF-κB pathway. Additionally, the sepsis resistant effects of HSP70 could be blocked by its antibody. In summary, more than a molecular chaperone to maintain homeostasis, HSP70 could be an important trained immunity inducer to help the body fighting against sepsis, which provided new stimuli for trained immunity and novel therapeutic solutions for sepsis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156861"},"PeriodicalIF":3.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997493","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":"M2 macrophage-targeting peptide-modified liposomes enhance the uptake and antitumor efficacy of liposomal IFN-γ in mice with C26 colon carcinoma","authors":"Maryam Kateh Shamshiri ,&nbsp;Roghayyeh Vakili-Ghartavol ,&nbsp;Hammed Tanimowo Aiyelabegan ,&nbsp;Zahra Asvar ,&nbsp;Hadi Zare Marzouni ,&nbsp;Maryam Matbou Riahi ,&nbsp;Mahmoud Reza Jaafari","doi":"10.1016/j.cyto.2025.156860","DOIUrl":"10.1016/j.cyto.2025.156860","url":null,"abstract":"<div><div>While liposomes enhance the safety and pharmacokinetic profile of free drugs, they have not significantly improved therapeutic efficacy. To overcome this challenge, targeted depletion of tumor-associated macrophages (TAMs) shows significant potential as an effective antitumor therapy, reducing off-target effects in comparison to non-targeted liposomes. In the context of peptide-mediated targeted cancer therapy, we evaluated the reprogramming activity of IFN-γ liposomes on TAMs, as well as that of IFN-γ liposomes modified with an M2 macrophage-targeting peptide, which binds preferentially to murine anti-inflammatory M2 macrophages/M2-like TAMs. Flow cytometry analysis showed significantly enhanced cellular uptake of m2-peptide-targeted liposomes in J774.1 macrophage cell lines compared to non-targeted liposomes. In BALB/c mice bearing C-26 murine carcinoma, the m2-peptide-targeted liposome groups exhibited significantly higher IFN-γ concentrations compared to non-targeted counterparts within the tumor environment. Furthermore, m2-peptide-targeted F2 liposomes at doses of 25 μg IFN-γ/kg resulted in superior tumor growth inhibition and greater tumor accumulation, indicating the potential of macrophage-targeted therapy in cancer growth inhibition. However, they failed to improve the overall therapeutic efficacy compared to Doxil. This study proposes a combination therapy of m2-peptide-targeted IFN-γ liposomes with successful chemotherapeutic liposomes such as Doxil.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156860"},"PeriodicalIF":3.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968880","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":"Smoking-induced shifts in salivary exosomal cytokines and amino acid profiles as potential early biomarkers for oral cancer","authors":"Afsareen Bano ,&nbsp;Ravina Vats ,&nbsp;Pooja Yadav ,&nbsp;Mala Kamboj ,&nbsp;Rashmi Bhardwaj","doi":"10.1016/j.cyto.2025.156857","DOIUrl":"10.1016/j.cyto.2025.156857","url":null,"abstract":"<div><h3>Background</h3><div>Chronic smoking is an established risk factor for oral cancer (OC). The role of tobacco in oral squamous cell cancer (OSCC) emphasizes the need for non-invasive diagnostic approaches to identify early molecular alterations and improve patient outcomes. Salivary exosomes, which contain proteins, lipids, and nucleic acids, accessible and rich in biological content, making them interesting candidate biomarkers.</div></div><div><h3>Methods</h3><div>Saliva samples were collected from non-smokers (<em>n</em> = 20), smokers (n = 20), and patients with oral cancer (n = 20). Salivary exosomes were isolated and characterized using various techniques, including estimation of protein concentrations and amino acid profiling using High-Performance Liquid Chromatography (HPLC). Fourier Transform Infrared (FTIR) spectroscopy analyzed protein and amino acid peaks, while enzyme-linked immunosorbent assay (ELISA) measured pro-inflammatory cytokines IL-6 and IL-8.</div></div><div><h3>Results</h3><div>Elevated levels of salivary exosomal proteins (<em>p</em> = 0.017), IL-6 (<em>p</em> = 0.008), and IL-8 (<em>p</em> = 0.0004), along with significant alterations in amino acid profiles, were observed in smokers compared with non-smokers. Additionally, protein (<em>p</em> = 0.005) and IL-6 (<em>p</em> = 0.004) levels were significantly elevated in oral cancer compared to non-smoker group. FTIR spectroscopy revealed distinct molecular fingerprints in exosomes, highlighting changes in protein and amino acid concentrations and indicating altered metabolism.</div></div><div><h3>Conclusion</h3><div>This comparative cross-sectional study demonstrated that chronic smoking induces significant biochemical changes in salivary exosomes, establishing them as promising non-invasive biomarkers for early oral cancer detection. Elevated pro-inflammatory cytokines IL-6 and IL-8, along with altered amino acid profiles, may create pre-cancerous conditions. Notably, along with altered amino acid profiles, IL-6 levels progressively increase from smoking to oral cancer, highlighting its potential role in cancer progression.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156857"},"PeriodicalIF":3.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968912","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":"Molecular mechanisms of transcription factor KLF4-mediated immune infiltration influencing lung adenocarcinoma invasion","authors":"Kaining Jia ,&nbsp;Yiwen Na ,&nbsp;Qiang Lin","doi":"10.1016/j.cyto.2024.156848","DOIUrl":"10.1016/j.cyto.2024.156848","url":null,"abstract":"<div><h3>Background</h3><div>Lung adenocarcinoma (LUAD) is associated with an increasing incidence and mortality rate while existing treatment strategies continue to exhibit considerable limitation. Studies have demonstrated that upregulation of KLF4 gene inhibits LUAD progression, but its underlying mechanisms remain elusive. The present research explored roles and mechanisms of KLF4 and the NF-κB pathway in LUAD.</div></div><div><h3>Methods</h3><div>Lentiviral vectors encoding KLF4 were constructed and transduced into H1299 and A549 cells to generate stable cell lines. These stable cell lines were then injected into BALB/c mice to establish a LUAD model. Subsequently, RNA sequencing, HE staining, immunohistochemistry, ELISA, Western blotting, and flow cytometry were employed to investigate the effects of KLF4 on tumor growth, invasion, immune cell infiltration, and related signaling pathways. Finally, dual-luciferase and in vivo mouse experiments were conducted to validate the molecular mechanisms.</div></div><div><h3>Results</h3><div>KLF4 significantly reduced tumor cell invasion while promoted tumor cell necrosis. Transcriptomic sequencing identified CXCR2 as a target gene and the NF-κB signaling pathway associated with immune infiltration regulation. KLF4 downregulated NF-κB2 and CXCR2 expression, concomitantly decreasing tumor cell invasiveness but increasing levels of CD4⁺ and CD8⁺ T cells and macrophages.</div></div><div><h3>Conclusion</h3><div>NF-κB and CXCR2 play an important role in KLF4-mediated immune infiltration, thereby inhibiting tumor invasion and promoting tumor cell apoptosis in mice.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156848"},"PeriodicalIF":3.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968883","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 diagnostic value and clinical correlations of bone marrow supernatant S100A8 and S100A9 in myelodysplastic neoplasms","authors":"Xuefeng Li,&nbsp;Qing Li,&nbsp;Xinrong Xiang,&nbsp;Xin Zhang,&nbsp;Yu Wu","doi":"10.1016/j.cyto.2025.156856","DOIUrl":"10.1016/j.cyto.2025.156856","url":null,"abstract":"<div><h3>Purpose</h3><div>Myelodysplastic neoplasms (MDS) are heterogeneous neoplasms that originate from bone marrow (BM) hematopoietic stem cells. S100A8 and S100A9 (S100A8/9) are crucial molecules involved in the innate immune pathogenesis of MDS. This study aimed to explore the value of these molecules in the differential diagnosis of MDS, and analyze the correlations between their concentrations and clinical characteristics.</div></div><div><h3>Methods</h3><div>We measured the concentrations of S100A8/9 in BM supernatant from patients newly diagnosed with MDS (<em>n</em> = 80) or aplastic anemia (AA) (<em>n</em> = 26) by enzyme-linked immunosorbent assay (ELISA). Correlations between clinical characteristics and S100A8/9 were explored based on patients' clinical information.</div></div><div><h3>Results</h3><div>Our study found the concentrations of S100A8/9 in the BM supernatant of MDS patients were significantly higher than those in AA patients (Both <em>P</em> &lt; 0.05). The concentrations of S100A8/9 in the group of very low/low/partial intermediate (IPSS-R score ≤ 3.5) risk MDS patients were also higher than those in AA patients (Both <em>P</em> &lt; 0.05). The serial or parallel diagnostic tests combining these two molecules for differentiating IPSS-R score ≤ 3.5 MDS and AA yielded high positive or negative predictive values, respectively. Moreover, the concentrations of S100A8/9 in MDS patients were positively correlated with the patients' age and the proportion of granulocytic series in BM (All <em>P</em> &lt; 0.05). Meanwhile, the concentrations of the two molecules had significantly negative correlations with the proportion of erythrocytic series in BM (Both <em>P</em> &lt; 0.05). However, intergroup differences in concentrations of S100A8/9 were not significant among different MDS risk groups, whether by IPSS-R or IPSS-M (All <em>P</em> &gt; 0.05).</div></div><div><h3>Conclusion</h3><div>The concentrations of S100A8/9 in BM supernatant have potential value in the differential diagnosis of MDS and AA. The correlations between the molecules' concentrations and clinical characteristics could provide new perspectives for future research in MDS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156856"},"PeriodicalIF":3.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968917","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":"Role of Interleukins-8, -17 and -22 in Iraqi postmenopausal women with Osteoporosis","authors":"Reem Salim Sultan Al-Lami ,&nbsp;Jabbar Hameed Yenzeel Al-Hilfy","doi":"10.1016/j.cyto.2024.156853","DOIUrl":"10.1016/j.cyto.2024.156853","url":null,"abstract":"<div><h3>Objectives</h3><div>Osteoporosis (OP) is a systemic skeletal disease characterized by low bone mineral density and deterioration of bone architecture, resulting in bone strength reduction and increased fracture susceptibility. Estrogen deficiency in post-menopausal women is possibly responsible for the instability between bone formation and resorption, which is managed by specific osteoclastogenic cytokines that may be leading to resorption. This study aims to estimation of the concentrations of interleukins −8, −17, −22, beside to certain parameters in blood serum and explained their roles in the development of osteoporosis pathogenicity in postmenopausal women.</div></div><div><h3>Materials and Methods</h3><div>A case-control study included 108 Iraqi postmenopausal women participants their ages ranged between 45 and 70 years. All participants subjected to the DEXA scan, 58 samples were osteoporotic patients, whereas 50 were healthy controls. Blood samples collected from all participants in order to assess the levels of interleukins −8, −17, −22, CBC, CRP, RF, and ACPA.</div></div><div><h3>Results</h3><div>The concentrations of IL-8, −17, −22, ESR, PLT, CRP, RF and ACPA exhibited a positive correlation with OP development. Conversely, WBC and HGB concentrations showed a negative association with osteoporosis.</div></div><div><h3>Conclusion</h3><div>A remarkable relationship was obtained between the values of IL-8, 17, −22, CRP, RF, ACPA, ESR, PLT and osteoporosis but in contrary with WBCs and HGB. IL-8, −17, and − 22 can be linked to specific inflammatory diseases associated with the postmenopausal period, may act as one of the main biomarkers for osteoporosis due to their ability to stimulate osteoclastogenesis and bone resorption, and may be considered potential prognostic factors for osteoporosis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156853"},"PeriodicalIF":3.7,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942114","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":"Prognostic value and clinical significance of IL-33 expression in patients with uterine corpus endometrial carcinoma","authors":"Yuqi Liu ,&nbsp;Han Wang ,&nbsp;Shihan Zhao ,&nbsp;Zhenjiang Wang ,&nbsp;Lijuan Yang ,&nbsp;Jihong Zhang ,&nbsp;Qinlong Hou ,&nbsp;ZiShen Xiao ,&nbsp;Pengmin Wang ,&nbsp;Yanbo Liu","doi":"10.1016/j.cyto.2024.156828","DOIUrl":"10.1016/j.cyto.2024.156828","url":null,"abstract":"<div><div>Uterine corpus endometrial carcinoma (UCEC) is one of the most common malignant tumours of the female genital tract. In the occurrence, progression and prognosis of UCEC, chronic inflammation plays an important role, making it pivotal to identify inflammatory response-related endometrial diseases. The cytokine interleukin-33 (IL-33) plays significant roles in immune responses, and has been associated with inappropriate allergic reactions, autoimmune diseases, and cancer pathology. In the past decade, studies have begun to uncover the pivotal roles of IL-33 in shaping tumour microenvironment (TME), where it may promote or inhibit tumorigenesis and development depending on the specific tumour types. However, the association between IL-33 expression and UCEC remains unclear. Here we investigated the expression profiles of IL-33 in pan-cancer based on TCGA database. Then, differential gene expression analysis and correlation analysis of IL-33 was investigated in UCEC. In addition, functional enrichment analysis and Kaplan–Meier survival analysis were performed to predict the potential function of IL-33 and its role in the prognosis of UCEC patients. Also, a nomogram model was constructed to predict the prognosis of UCEC. The expression of the inflammatory factor NF-κB p65 and the IL-33, along with its receptor ST2, was analyzed in UCEC tumour tissues and normal tissues of clinical specimens through immunohistochemical staining. Meanwhile, we used toluidine blue staining and methanol Congo red staining to observe the infiltration of mast cells and eosinophils in the endometrial tissue. The results of Kaplan–Meier plotter data indicated that patients with lower IL-33 expression had poorer progression-free interval than those with higher expression. Based on the results of multifactor Cox regression, a nomogram was generated to predict UCEC occurrence risk and prognosis. Clinical specimen characteristics also confirmed a negative correlation between IL-33 expression and UCEC staging and grading. This comprehensive analysis of IL-33, based on bioinformatics and immunohistochemistry, revealed that IL-33 has the function of inhibiting UCEC occurrence and progression and can be served as a beneficial prognostic marker in the clinic.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156828"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805661","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":"Unveiling the nexus: The tumor microenvironment as a strategic frontier in viral cancers","authors":"Queenie Fernandes ,&nbsp;Oginni Gbenga Folorunsho","doi":"10.1016/j.cyto.2024.156827","DOIUrl":"10.1016/j.cyto.2024.156827","url":null,"abstract":"<div><div>Viral infections are a significant factor in the etiology of various cancers, with the tumor microenvironment (TME) playing a crucial role in disease progression. This review delves into the complex interactions between viruses and the TME, highlighting how these interactions shape the course of viral cancers. We explore the distinct roles of immune cells, including T-cells, B-cells, macrophages, and dendritic cells, within the TME and their influence on cancer progression. The review also examines how viral oncoproteins manipulate the TME to promote immune evasion and tumor survival. Unraveling these mechanisms highlights the emerging paradigm of targeting the TME as a novel approach to cancer treatment. Our analysis provides insights into the dynamic interplay between viruses and the TME, offering a roadmap for innovative treatments that leverage the unique characteristics of viral cancers.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156827"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794146","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":"NK cell-derived exosomes inhibit survival of Mycobacterium tuberculosis by promoting apoptosis in mice.","authors":"Yumei Dai, Xuan Wang, Wenya Du, Ruifeng Chen, Fengqian Ma, Tao Ma, Linzhi Yue, Tongrui Fang, Guofu Wang, Ling Geng, Tao Wang, Lixian Wu","doi":"10.1016/j.cyto.2024.156820","DOIUrl":"10.1016/j.cyto.2024.156820","url":null,"abstract":"<p><strong>Aim: </strong>To investigate anti-Mycobacterium tuberculosis (Mtb) influences exerted by natural killer cell-derived exosomes (NK-exo) on mice and to elucidate underlying immunologic mechanisms.</p><p><strong>Methods: </strong>We established tuberculosis (TB) model in mouse by injecting Mtb H37Ra (1 × 10⁶ colony counting (CFU), i.v.) into tail vein for 14 days. The survival rate of Mtb was assessed through CFU, apoptosis rates were measured utilizing flow cytometry, and inflammation relief was quantified via HE staining. Expressions of apoptosis, inflammation, and pyroptosis-related proteins were quantified by Western blotting and RT-qPCR. ELISA was utilized for detecting inflammatory cytokines production. Intracellular reactive oxygen species (ROS) levels were assessed through DCFH-DA fluorescent probe assay.</p><p><strong>Results: </strong>NK-exo treatment reduced Mtb load in lung and spleen tissues and alleviated inflammation in mice lung tissues. NK-exo intervention increased protein levels of markers associated with apoptosis, PARP and caspase-3/8/9, downregulating the concentrations of pro-inflammatory cytokines, comprising IL-1β, TNF-α, IL-6, along with protein expressions of biomarkers, ASC, NLRP3, GSDMD, associated to inflammation and pyroptosis. NK-exo also elevated ROS levels without affecting lactate dehydrogenase (LDH) release from macrophages.</p><p><strong>Conclusion: </strong>NK-exo exhibits anti-tuberculosis activity in experimental TB mice. The underlying mechanism involve regulating caspase-dependent apoptotic signaling pathway to promote cell apoptosis, as well as modulating NLRP3 signaling pathway to suppress the inflammatory response.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"156820"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754398","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}