Cytokine最新文献

{"title":"Unveiling the nexus: The tumor microenvironment as a strategic frontier in viral cancers.","authors":"Queenie Fernandes, Oginni Gbenga Folorunsho","doi":"10.1016/j.cyto.2024.156827","DOIUrl":"10.1016/j.cyto.2024.156827","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"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":"","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, Han Wang, Shihan Zhao, Zhenjiang Wang, Lijuan Yang, Jihong Zhang, Qinlong Hou, ZiShen Xiao, Pengmin Wang, Yanbo Liu","doi":"10.1016/j.cyto.2024.156828","DOIUrl":"10.1016/j.cyto.2024.156828","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"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":"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}

{"title":"Impact of oral flora in tongue coating and saliva on oral cancer risk and the regulatory role of Interleukin-8.","authors":"Xiaotang Wang, Xiaona Song, Jiping Gao, Yunhui Ma, Tian Wang, Xiaoqi Chang, Shuxuan Shi, Yaqi Liu, Guohua Song","doi":"10.1016/j.cyto.2024.156821","DOIUrl":"10.1016/j.cyto.2024.156821","url":null,"abstract":"<p><strong>Background: </strong>Oral flora and inflammatory factors play a crucial role in oral cancer, but the relationship between them and oral cancer has not been clearly established.</p><p><strong>Methods: </strong>Oral flora served as exposure factor, oral cancer as outcome factor, and inflammatory factors as mediating factor. Mendelian randomization (MR) analysis was used to analyze the relationship between oral flora and oral cancer, and the potential mediating effect of inflammatory factors was explored through mediation analysis.</p><p><strong>Results: </strong>29 kinds of oral flora in tongue coating and 22 kinds of oral flora in saliva were associated with increased risk of oral cancer. 18 species of oral flora in tongue coating and 25 species in saliva were associated with a reduced risk of oral cancer. Interleukin-8 (IL8) played a mediating role in the relationship between oral flora and oral cancer, and it was associated with an increased risk of oral cancer. Granulicatella, Streptococcus mitis, Saccharimonadaceae and Haemophilus in oral flora caused oral cancer indirectly through IL8. IL8 expression increased in oral cancer, which has good diagnostic value. IL8-related genes in oral cancer are closely associated with immune cell infiltration. What's more, IL8 has potential medicinal properties.</p><p><strong>Conclusion: </strong>Oral flora of tongue coating and saliva is closely related to oral cancer, and IL8 plays a mediating role in the causal relationship between oral flora and oral cancer.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"156821"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778711","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 effect of long-term exposure to moderate high altitude on adipokines and insulin sensitivity.","authors":"Wenxia Wu, Guishan Chen, Xiaoyun Zhang, Hongshi Wu, Yu-E Wang, Xin Li, Ying Liang, Dan Liu","doi":"10.1016/j.cyto.2024.156823","DOIUrl":"10.1016/j.cyto.2024.156823","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;High altitude area refers to plateau area with an altitude of 1500 m or above. Short-term (less than 30 days) exposure to high-altitude environments (hypoxia, low temperature, low pressure) might affect the adipokines level and insulin sensitivity. However, whether long-term exposure to moderate high altitude would have an impact on adipokines and insulin sensitivity remains unknown.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to explore the effect of long-term exposure (12 months) to moderate high altitudes (2900 m) on changes in adipokines level and insulin sensitivity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;48 healthy adults from Guangdong Province (the average altitude less than 50 m) to Nyingchi (an average altitude of 2900 m) were included with follow-up of 12 months. Before entering Nyingchi, baseline anthropometric indicators (height, weight, blood pressure), metabolic indicators: fasting plasma glucose (FPG), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR), adipokines: adiponectin and leptin, inflammatory indicators: tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6); hypoxia-inducible factor 1alpha (HIF-1α), oxidative stress indicator: malondialdehyde (MDA), antioxidant indicators: superoxide dismutase (SOD) and glutathione (GSH) were determined. After entering Nyingchi, the above indicators were retested at the 1st, 6th, and 12th month. The control group consist of 47 local residents in Nyingchi. Linear mixed effect model was used to analyze the trend of index changes. Multivariate linear regression analysis was analyzed to explore the influence factors of adiponectin at 12th month.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;After 12 months exposure to high altitude, the body mass index (BMI), systolic blood pressure (SBP) and FPG of subjects decreased from baseline of 23.51 ± 2.68 kg/m&lt;sup&gt;2&lt;/sup&gt;, 123.68 ± 14.94 mmHg and 5.05 ± 0.36 mmol/L to 22.59 ± 2.56 kg/m&lt;sup&gt;2&lt;/sup&gt;, 116.10 ± 14.68 mmHg and 4.65 ± 0.46 mmol/L respectively, HDL-C increased from baseline of 1.30 ± 0.26 mmol/L to 1.37 ± 0.30 mmol/L. HOMA-IR decreased from baseline 1.70 (1.19, 2.22) to 1.25(1.04, 1.78). Adiponectin increased from 3.85(3.05, 4.98) to 4.75(3.33, 5.88) μg/mL, leptin decreased from 1022.10(496.30, 2508.60) to 729.60(308.78, 1670.20) pg/mL. TNFα decreased from 6.81(5.37, 8.49) to 5.50(4.00, 6.74) pg/mL. The level of HIF-1α increased from baseline 1.91 (1.32, 5.09) to 2.94 (1.65, 15.45) pg/mL. SOD increased from 0.20(0.15, 0.24) to 0.25(0.20, 0.28) U/mL. Multivariate linear regression analysis showed that HIF-1α (β = 0.006, 95 %CI, 0.001-0.012, p = 0.033) and SOD (β = 7.318, 95 %CI, 0.486-14.149, p = 0.037) was the factors that influenced adiponectin level at 12th month after exposure to high altitude.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Long-term exposure to moderate high-altitude environments could improve insulin sensitivity and adipocyte function in healthy adults. Elev","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"156823"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764957","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":"Effects of probiotics on clinical manifestations and inflammatory markers in HTLV-1-associated myelopathy/tropical spastic paraparesis: A triple blind randomized, placebo controlled trial.","authors":"Parvaneh Mamaghani Rad, Zohreh Vahidi, Mostafa Zemorshidi, Mohammad Taghi Farzadfard, Majid Khadem-Rezaiyan, Reza Boostani, Mohammad Ali Nahayati, Houshang Rafatpanah, Fariba Zemorshidi","doi":"10.1016/j.cyto.2024.156825","DOIUrl":"10.1016/j.cyto.2024.156825","url":null,"abstract":"<p><p>Human T-lymphotropic virus type 1 (HTLV-1), leads to adult T-cell lymphoma/leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a minority of infected individuals. The virus promotes inflammation, a major factor in chronic disease progression. Probiotics' immune modulation and anti-inflammatory effects present a potential therapeutic intervention for HTLV-1-related conditions. This study investigates the impact of probiotics on both clinical manifestations and inflammatory markers in HAM/TSP patients. Conducted at the HTLV-1 clinic of Ghaem Hospital (Mashhad, Iran) between 2019 and 2020, this study randomized 40 HAM/TSP patients into two groups: an intervention group receiving 500 mg LactoCare capsules twice daily and a control group receiving placebo capsules of identical appearance for 12 weeks. Baseline and follow-up assessments included muscle strength, spasticity, motor disability, urinary disturbance, and serum levels of IL-10, IL-4, and IFN-γ (measured by ELISA). Post-intervention analysis revealed no significant differences between intervention and control groups in muscle strength, spasticity, and motor disability. However, significant improvement was observed in the intervention group regarding urinary symptoms after 12 weeks of initiation of intervention (P = 0.003). No significant changes were detected in serum levels of IL-10, IL-4, and IFN-γ between the two groups. The probiotics showed positive effects on urinary symptoms in HTLV-1-associated myelopathy/tropical spastic paraparesis patients but did not significantly impact other clinical or paraclinical parameters within the 12-week study period. These findings suggest that probiotics may offer symptomatic relief for some symptoms of HTLV-1-associated myelopathy/tropical spastic paraparesis patients.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"156825"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778707","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":"Unraveling the causal associations between systemic cytokines and six inflammatory skin diseases.","authors":"Waner Liu, Xu Zhang, Xiang Chen","doi":"10.1016/j.cyto.2024.156810","DOIUrl":"10.1016/j.cyto.2024.156810","url":null,"abstract":"<p><strong>Background: </strong>Previous observational studies have reported that systemic cytokines are associated with the risk of inflammatory skin diseases, but their conclusions remain controversial.</p><p><strong>Method: </strong>We conducted a two-sample Mendelian randomization analysis to assess the relationship between systemic cytokines and six inflammatory skin disorders (including alopecia areata (AA), acne, atopic dermatitis (AD), hidradenitis suppurativa (HS), psoriasis (PS) and vitiligo), based on datasets from EArly Genetics and Lifecourse Epidemiology (EAGLE) eczema consortium, acne GWAS conducted by Maris Teder Laving et al., IEU Open GWAS, and FinnGen database. Inverse-variance weighted (IVW) method was conducted in primary MR analysis, and supplemented by MR-Egger, weighted median, weighted mode, and MR-PRESSO.</p><p><strong>Results: </strong>By integrating the findings from both primary and sensitivity analyses, we identified ten systemic cytokines linked to the risk of six skin diseases using the IVW method. Briefly, four cytokines increased the risk of corresponding skin diseases: β-nerve growth factor (β-NGF) to AA (p = 0.005) and HS (p = 0.001), interleukin-8 (p = 0.014) to acne; interleukin-5 (p = 0.042) to AD; interleukin-13 (p = 0.049) to PS. In the meantime, seven cytokines could have protective effect on specific skin diseases: interleukin-9 (p = 0.040) and interleukin-2 receptor subunit alpha (IL-2ra) (p = 0.020) on AA; macrophage inflammatory protein (MIP)-1β (p = 0.020) on acne; monokine induced by IFN-γ (p = 0.006) on AD; interleukin-16 (p = 0.038), MIP-1β (p = 0.017) and IL-2ra (p = 0.020) on PS.</p><p><strong>Conclusions: </strong>This study reveals 13 causal associations between systemic cytokines and 6 skin diseases, offering new perspectives on the prevention and management of widespread inflammatory skin disorders.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"156810"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778714","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":"Anti-CD8/IL-15 (N72D)/sushi fusion protein: A promising strategy for improvement of cancer immunotherapy.","authors":"Nafiseh Maghsoodi, Mohammadrasul Zareinejad, Abbas Ghaderi, Elham Mahmoudi Maymand, Cambyz Irajie, Amin Ramezani","doi":"10.1016/j.cyto.2024.156822","DOIUrl":"10.1016/j.cyto.2024.156822","url":null,"abstract":"<p><strong>Background: </strong>To overcome the limitations of IL-15 and to improve the efficacy of IL-15 in immunotherapy, several strategies have been introduced.</p><p><strong>Objective: </strong>The objective of this study was to generate and evaluate a novel anti-CD8/IL-15 (N72D)/Sushi fusion protein with the potential to target CD8⁺ T cells and enhance functionality of CD8⁺ T cells against tumor cells.</p><p><strong>Methods: </strong>In this connection, a novel fusokine that contains IL-15(N72D), a Sushi domain, and anti-CD8 single-chain fragment variable (scFv) was designed. The size accuracy and binding potency of the isolated protein were assessed using western blotting and indirect surface staining. Following purification, the potential function of the anti-CD8/IL-15(N72D)/Sushi fusion protein in the induction of proliferation and cytotoxicity of CD8⁺ T cells was evaluated.</p><p><strong>Results: </strong>In-silico analysis revealed that fusokine is structurally stable, correctly folded and can interact with the CD8 co-receptor. Both fusokine and IL-15(N72D)/Sushi were produced in CHO-S cell line with a final concentration of 18.43 mg/l and 12.64 mg/l respectively. Fusokine bound to 97.6 % of CD8⁺ T cells and significantly induced T cell proliferation and cytotoxic potential in peripheral blood mononuclear cells (PBMCs) in a time dependent manner. Compared to both the control and the IL-15 (N72D)/sushi treated groups, fusokine showed superior potential in CD8⁺ T cell functionality.</p><p><strong>Conclusion: </strong>Anti-CD8/IL-15(N72D)/Sushi has the ability to effectively target CD8⁺ T cells, promote lymphocyte proliferation and induce cytotoxicity against tumor cells. Due to its promising properties, it could be considered as a new potential immunotherapy approach.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"156822"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778704","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 protective effect of the vagus nerve-α7nAChR-IL-22 pathway on acute liver injury.","authors":"Zhihao Song, Jing Wu, Tiemin Jiang, Rongdong He, Hao Wen","doi":"10.1016/j.cyto.2024.156840","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156840","url":null,"abstract":"<p><strong>Background: </strong>Acute liver injury is a common pathological feature of various clinical diseases, and prolonged liver damage can lead to fibrosis and even liver failure. Studies have reported that the vagus nerve can repair liver injury through the regulation of the cholinergic anti-inflammatory pathway. However, there is limited research on the regulation of interleukin-22 and its role in liver injury. This study aimed to investigate the regulatory effect of vagus nerve receptor α7nAChR on interleukin-22 and whether this regulatory axis can protect against liver injury.</p><p><strong>Methods: </strong>Rats and the human liver cell line L-02 were treated with carbon tetrachloride to simulate acute liver injury. The experimental groups were divided as follows: control group, model group, model + PNU282987 group, model + MLA group, and MLA group. After the intervention, blood samples, liver tissues, and cells were collected to assess liver function (AST, ALT), inflammation (TNF-α, IL-6,), α7nAChR and interleukin-22 concentrations, apoptosis levels (Bax, BCL-2), and proliferation markers (Ki-67, PCNA) using quantitative real time PCR, Western blot, immunohistochemistry and ELISA.</p><p><strong>Results: </strong>The results indicated that carbon tetrachloride intervention led to compensatory increases in interleukin-22 while inhibition of α7nAChR decreased interleukin-22 concentrations and exacerbated the injury marked by high levels of AST, ALT and TNF-α,IL-6. Exogenous administration of a vagus nerve agonist alleviated liver injury and was accompanied by an increase in interleukin-22 levels. In rescue experiments, simultaneous inhibition of vagus nerve receptors and administration of exogenous interleukin-22 reduced liver injury and significantly enhanced liver regeneration. Conversely, activation of vagus nerve receptors while inhibiting interleukin-22 aggravated liver injury.</p><p><strong>Conclusion: </strong>This study confirms that vagus nerve receptor α7nAChR can promote liver regeneration and protect against carbon tetrachloride-induced liver injury by regulating interleukin-22.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"156840"},"PeriodicalIF":3.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870774","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":"Influence of head and neck cancer exosomes on macrophage polarization.","authors":"Joni Yadav, Tanya Tripathi, Apoorva Chaudhary, Divya Janjua, Udit Joshi, Nikita Aggarwal, Arun Chhokar, Chetkar Chandra Keshavam, Anna Senrung, Alok Chandra Bharti","doi":"10.1016/j.cyto.2024.156831","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156831","url":null,"abstract":"<p><strong>Background: </strong>Tumor cells within the tumor microenvironment (TME) release exosomes that influence macrophage phenotypes, either pro-tumorigenic or anti-tumorigenic. This mechanism, especially in head and neck squamous cell carcinoma (HNSCC), remains poorly understood. This study investigates the role of HNSCC exosomes in macrophage polarization.</p><p><strong>Methodology: </strong>Exosomes were isolated from HPV16-positive (93VU147T, UDSCC2) and HPV-negative (OCT1) HNSCC cell lines. These exosomes were characterized for their potential to modulate macrophage polarization. Uptake of PKH-26 labeled exosomes by macrophages was monitored via confocal microscopy. Changes in macrophage polarization were assessed using quantitative real-time PCR and immunoblotting. Exosomal transcripts and proteome cargo was examined for polarization associated mediators.</p><p><strong>Results: </strong>HPV-negative exosomes showed higher uptake by THP1 resting macrophages (M0). Exosomes from HPV-positive cells induced a mixed macrophage phenotype (M1 and M2), whereas HPV-negative exosomes favored M1 polarization. Immunoblotting analysis revealed that this polarization was driven by the activation of transcription factors STAT1, NF-κB, and AP1. Transcriptomic analysis of HNSCC exosomes revealed reads for AP1 (c-Jun, c-Fos, FosB, Fra1, Fra2) and NF-κB (p50/105, p52/100, RelA, RelB, c-Rel), along with their known upstream mediators MEK1--7, JNK1-3, JAK1-3, TYK2, IKKα, and IKKβ. Splice variants of macrophage polarization markers, including iNOS and TGFβ, were also identified, though none of the exosomal proteome component corresponded to these factors.</p><p><strong>Conclusion: </strong>HPV-negative exosomes are efficiently internalized by macrophages, promoting M1 polarization likely via modulation of STAT1, NF-κB, and AP1 signaling. These findings provide novel insights into role of tumor exosomes in modulation of macrophage-mediated TME dynamics in HNSCC.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"156831"},"PeriodicalIF":3.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862592","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}