Cytokine最新文献

{"title":"Interleukin-4 ameliorates macrophage lipid stress through promoting cholesterol efflux and lipid homeostasis","authors":"Kuo-Ting Ho ,&nbsp;Fang-Yeh Chu ,&nbsp;Yi-Kai Lin ,&nbsp;Ho-Hsun Chin ,&nbsp;Shun-Chun Yang ,&nbsp;Ching-Ping Yang ,&nbsp;Yih-Hsin Chang","doi":"10.1016/j.cyto.2025.156869","DOIUrl":"10.1016/j.cyto.2025.156869","url":null,"abstract":"<div><div>Over-nutrition and lipid metabolic abnormalities are correlated with obesity and type 2 diabetes mellitus (T2DM). Individuals with long-term hyperglycemia and dyslipidemia are susceptible to life-threatening complications such as atherosclerosis. Excess amounts of modified low density lipoprotein (mLDL) attract circulating monocytes to resident at arterial wall and differentiate into pro-inflammatory M1 macrophages. M1 cells uptake mLDL through scavenger receptors-mediated endocytosis, leading to increased lipids influx, cholesterol accumulation and foam cell formation. Besides, macrophages are attracted and infiltrated into the hypertrophic adipose tissue to mediate microenvironmental lipid metabolism. Our previous studies demonstrate that anti-inflammatory interleukin-4 (IL-4) regulates lipid metabolism by inhibiting lipid accumulation and promoting lipolysis of mature adipocytes. The effects of IL-4-polarized M2 macrophages on 3T3-L1 adipogenesis and macrophage-adipocyte interaction were explored in the present study. Our results showed lipid deposits and lipid droplets (LDs)-anchored perilipin of adipocytes cultured in IL-4-polarized M2-conditioned medium (M2-CM) were decreased, while adipogenesis-driving transcription factors and critical lipid metabolic enzymes remained unaffected. It indicates that M2-secreted mediators down-regulate lipid deposits and LDs formation in late adipogenic phase rather than interfering early programming phase and lipid synthesis machinery. In addition, IL-4 reduced intracellular lipid loads by up-regulating cholesterol efflux ATP-binding cassette transporter A1 (ABCA1) and ABCG1 despite cholesterol influx CD36 was also elevated. Accordingly, IL-4 shows beneficial effects to prevent atherosclerosis via promoting catabolism of the internalized lipids and cholesterol efflux, thus efficiently reduces lipid overload and foam cell formation. These findings illustrate novel roles and protective function of IL-4 to reduce the risk of atherosclerosis incidence by efficiently promoting macrophage cholesterol efflux and lipid homeostasis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156869"},"PeriodicalIF":3.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419772","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":"A pilot investigation on inflammatory markers and theta burst stimulation protocol interaction along a three-month recovery course following an isolated upper limb fracture","authors":"Bénédicte Robitaille ,&nbsp;Alberto Herrero Babiloni ,&nbsp;Marianne Jodoin ,&nbsp;Marie-Michèle Briand ,&nbsp;Dominique M. Rouleau ,&nbsp;Louis De Beaumont","doi":"10.1016/j.cyto.2025.156885","DOIUrl":"10.1016/j.cyto.2025.156885","url":null,"abstract":"<div><div>This study investigates the effects of theta burst stimulation (TBS) on inflammatory markers in patients with isolated upper limb fractures (IULF). Participants underwent a 10-day TBS intervention following a randomized matched pair design. Blood samples collected at three time points were analyzed for inflammatory biomarkers, mainly including interleukin-1 receptor antagonist (IL-1Ra), IL-1β, and IL-6. Results revealed a significant interaction between TBS and time for IL-1Ra, indicating a more pronounced decrease in IL-1Ra expression over time in the active TBS group. However, IL-6 levels decreased over time regardless of TBS intervention, suggesting a natural decline in response to injury. No significant interaction was found for IL-1β. While IL-1Ra levels were associated with higher functional disability prior to treatment initiation, active TBS intervention led to a decrease of IL-1Ra levels at both follow-up time points. These changes were not associated with alterations in pain or disability, suggesting that TBS may primarily influence recovery processes independent of pain modulation. Notably, IL-1β levels were negatively correlated with disability in the active TBS group at the 3-month follow-up. This study sheds light on the potential of TBS to modulate inflammatory responses in orthopedic trauma, emphasizing the need for further research to elucidate its therapeutic implications. Clinical Significance: TBS may offer a promising adjunctive therapy for promoting functional recovery in patients with upper limb fractures.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156885"},"PeriodicalIF":3.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388360","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":"Prognostic valule of vasoactive drug score, NT-proBNP, and blood lactate level at 6 h post-admission in adult sepsis patients:A single-center, retrospective study","authors":"Xiaokang Peng ,&nbsp;Fang Ye ,&nbsp;Jiao Wang ,&nbsp;Linnan Li ,&nbsp;Chenghua Wang ,&nbsp;Hongfeng Yang","doi":"10.1016/j.cyto.2025.156891","DOIUrl":"10.1016/j.cyto.2025.156891","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Sepsis is a prevalent and critical condition triggered by an exaggerated immune response to specific infectious agents. The classification of the severity of sepsis plays a fundamental role in early identification and structured management, aiding in the prediction of increased risk of mortality. Despite the utilization of numerous biomarkers in sepsis diagnosis and treatment guidance, the early identification and prediction of sepsis still pose significant challenges.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To assess the prognostic value of vasoactive-inotropic score (VIS), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and 6 h blood lactate after admission in adult sepsis patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;177 adult sepsis patients were enrolled in a cross-sectional study. Based on their 28-day outcome upon admission, patients were divided into a death group (&lt;em&gt;n&lt;/em&gt; = 52) and a survival group (&lt;em&gt;n&lt;/em&gt; = 125). Clinical data from both groups were collected. Univariate analysis and binary logistic regression were employed to identify independent risk factors for poor prognosis in adult sepsis patients. Receiver operating characteristic curve (ROC) analysis was performed to determine the predictive value of VIS, NT-proBNP, and blood lactate level at 6 h after admission for adult sepsis patients. Kaplan-Meier method was utilized to analyze the relationship between VIS, NT-proBNP, blood lactate level at 6 h after admission, and survival prognosis among adult sepsis patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;1. VIS (OR: 7.117; 95 % CI: 1.648–30.738; &lt;em&gt;P&lt;/em&gt; = 0.009), NT-proBNP (OR: 1.296; 95 % CI: 1.026–1.637; &lt;em&gt;P&lt;/em&gt; = 0.030), SOFA score (OR:1.232; 95 % CI: 1.031–1.473; P = 0. 02) and blood lactate at 6 h after admission (OR: 3.484; 95 % CI: l.416–8.573; &lt;em&gt;p&lt;/em&gt; = 0.007) were independent risk factors for poor prognosis of adult sepsis. 2. VIS, NT-proBNP, and blood lactate at 6 h after admission were positively correlated with SOFA scores (&lt;em&gt;r&lt;/em&gt; = 0 0.255, 0.388, and 0.l89 respectively, &lt;em&gt;P&lt;/em&gt; &lt; 0.05). 3. ROC curve analysis showed that the area under the curve (AUC) of VIS, NT-proBNP, and blood lactate at 6 h after admission for predicting poor prognosis in adult sepsis patients was 0.673, 0.790, and 0.702 respectively. When the cut-off values were 3.86, l.69,and 3.35, the sensitivity was 40.5 %, 71.8 %, and 59.3 %, the specificity was88.2 %, 65.8 %, and 72.9 %, and the Youden index was 0.288, 0.501, and 0.324, respectively. 3. Kaplan-Meier analysis revealed statistically significant differences in survival prognosis between patients with VIS &gt;1.69 and VIS ≤1.69 (Log-rank χ&lt;sup&gt;2&lt;/sup&gt; = 18.404, &lt;em&gt;P&lt;/em&gt; &lt; 0.001), NT-proBNP &gt;3.86 and NT-proBNP ≤3.86 (Log-rank χ&lt;sup&gt;2&lt;/sup&gt; = 38.282, P &lt; 0.001), as well as blood lactate &gt;3.35 and blood lactic acid ≤3.35 after a duration of 6 h from admission (Log-rank χ&lt;sup&gt;2&lt;/sup&gt; = 11.776, P &lt; 0.001).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156891"},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377480","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":"Maternal cytokine and cellular adhesion molecules profile in pregnant women with and without congenital heart disease.","authors":"Francois Dos Santos,&nbsp;Philip J. Steer,&nbsp;Mark R. Johnson","doi":"10.1016/j.cyto.2025.156886","DOIUrl":"10.1016/j.cyto.2025.156886","url":null,"abstract":"<div><h3>Introduction</h3><div>Despite corrective surgery, patients with congenital heart disease (CHD) have residual regions of disturbed oscillatory blood flow which can induce upregulation of proinflammatory cytokines and adhesion molecules. Data on cytokine and cellular adhesion molecule (CAM) profiles in low risk pregnancy and pregnancy complicated by CHD are limited. The objective of this work was to study the profile of IL-6, IL-10, TNFα, ghrelin, GRO<em>α</em>, and ICAM/VCAM in pregnancy in women with and without CHD and test the hypothesis that the circulating levels of these are correlated with obstetric outcomes.</div></div><div><h3>Methods</h3><div>Prospective study of women ≥18 years carrying a singleton low risk pregnancy low-risk (LR-group) and pregnant women with CHD (CHD-group). Study visits were conducted between 10 and 14, 18–22 and 30–34 weeks' gestation with blood sampling for immune profiling using the <em>Bio-Plex® Multiplex Immunoassay</em>. The immune profile was investigated in both groups and correlated with obstetric outcomes. This study was approved by the Health Research Authority and the London South East Research Ethics Committee (REC reference: 17/LO/0970).</div></div><div><h3>Results</h3><div>Forty-five samples in 30 participants with CHD and 45 gestational age-matched samples from 34 low-risk pregnant women were analysed. Women in the CHD-group delivered earlier (38 + 6 weeks <em>vs</em> 39 + 4 weeks, <em>p</em> = 0.005) and had smaller babies (2940 g, 30.0 centile <em>vs</em> 3415 g, 63.5 centile, <em>p</em> &lt; 0.001). There were no significant differences in the levels of IL-6, IL-10 or TNFαin both groups across trimesters. Levels of GRO<em>α</em> increased in both groups but less so in the CHD group. Levels of ghrelin decreased in both groups but less so in the CHD group. Levels of ICAM decreased as pregnancy progressed in the CHD group. Levels of VCAM increased in both groups but more significantly in the CHD-group (second trimester, <em>p</em> &lt; 0.001; third trimester, <em>p</em> = 0.045). Women in the CHD-group had higher levels if IL-6 (<em>p</em> = 0.005) and ICAM (p &lt; 0.001) lower levels of IL-10 in the third trimester (<em>p</em> = 0.018). There was a significant positive association between levels of IL-6 in the first trimester and birthweight centiles (r_s = 1.00, <em>p</em> &lt; 0.001) in the CHD group.</div></div><div><h3>Conclusion</h3><div>There was minimal fluctuation in the levels of the studies cytokines during pregnancy with exception of GRO<em>α</em> and ghrelin, both implicated in fetal growth. Women with CHD had higher levels of proinflammatory cytokines and ICAM in the first trimester, and lower levels of IL-10 in the third trimester, suggesting a more proinflammatory state. High levels of VCAM in the CHD group could be secondary to endothelial activation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156886"},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378619","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 NLR pathway signatures: EP300 and CPN60 markers integrated with clinical data and machine learning for precision NASH diagnosis","authors":"Marwa Matboli ,&nbsp;Noha E. El-Attar ,&nbsp;Ibrahim Abdelbaky ,&nbsp;Radwa Khaled ,&nbsp;Maha Saad ,&nbsp;Amani Mohamed Abdel Ghani ,&nbsp;Eman Barakat ,&nbsp;Reginia Nabil Mikhail Guirguis ,&nbsp;Eman Khairy ,&nbsp;Shaimaa Hamady","doi":"10.1016/j.cyto.2025.156882","DOIUrl":"10.1016/j.cyto.2025.156882","url":null,"abstract":"<div><h3>Background</h3><div>Given the increasing prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic steatohepatitis (NASH), there is a critical need for accurate non-invasive early diagnostic markers.</div></div><div><h3>Objective</h3><div>This study aimed to validate NLRP3-related RNA signatures (EP300, CPN60, and ITGB1 mRNAs, miR-6881-5p, and LncRNA-RABGAP1L-DT-206) using an integrated molecular approach and advanced machine-learning algorithms to identify robust biomarkers for early diagnosis of NASH.</div></div><div><h3>Methods</h3><div>A cohort of 237 participants (117 Healthy controls, 60 MAFLD, 120 NASH) was utilized. Twenty-five demographic, clinical, and molecular features were collected from each participant. Various machine learning models were trained on the dataset.</div></div><div><h3>Results</h3><div>The Random Forest algorithm emerged as the most effective classifier. The model identified nine key features: EP300 mRNA, CPN60 mRNA, AST, D. bilirubin, Albumin, GGT, HbA1c, HOMA-IR, and BMI, achieving an impressive 97 % accuracy in distinguishing NASH from non-NASH cases.</div></div><div><h3>Conclusion</h3><div>The integration of molecular, clinical, and demographic data with machine learning algorithms provides a highly accurate method for the early diagnosis of NASH. This model holds promise for early detection in individuals at risk of progressing to cirrhosis or liver cancer and may aid in identifying new therapeutic targets for managing NASH.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156882"},"PeriodicalIF":3.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350707","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":"Different IL-1β levels differentially mediate neuroprotection or neurodegeneration and may be related to BDNF","authors":"Sifan Long ,&nbsp;Yanmei Wang ,&nbsp;Rong Cheng ,&nbsp;Liuyuan Deng ,&nbsp;Lixing Chen ,&nbsp;Yilong Dong","doi":"10.1016/j.cyto.2025.156877","DOIUrl":"10.1016/j.cyto.2025.156877","url":null,"abstract":"<div><h3>Background</h3><div>The detrimental and protective effects of interleukin 1β (IL-1β) have been reported. We have previously shown that the periods of IL-1β elevation is related to its dual effects. However, the effects of different IL-1β concentrations on neuropathological processes are unclear. Studies have demonstrated that mature brain-derived neurotrophic factor (mBDNF) and its precursor (proBDNF) have opposing functions in neuronal survival. We previously showed that mBDNF is involved in IL-1β-mediated neuropathology. Here, we investigated whether different IL-1β concentrations differentially affect mBDNF and proBDNF, determining their beneficial or harmful effects.</div></div><div><h3>Methods</h3><div>HT22 cells were cultured and exposed to various IL-1β concentrations for different durations. HT22 cell viability and the expression of mBDNF, proBDNF and their receptors were evaluated by a Cell Counting Kit-8 (CCK-8) assay and western blot.</div></div><div><h3>Results</h3><div>Compared with untreated cells, a significant reduction in cell viability was observed after exposure to high IL-1β concentrations for more than 24 h. Increased expression of proBDNF and its receptor p75NTR and decreased expression of mBDNF and its receptor TrkB, as well as decreased furin and PC1/3 (which promote the cleavage of proBDNF to mBDNF) expression, were detected. In contrast, low IL-1β concentrations increased cell viability, but a significant effect was observed only at an optimal concentration; in contrast to our predictions, low IL-1β concentrations did not induce significant alterations in mBDNF and proBDNF expression levels, but rather, low concentrations significantly increased the mBDNF/proBDNF ratio.</div></div><div><h3>Conclusions</h3><div>These results demonstrated that changes induced by low (neuroprotection) and high (neurodegeneration) IL-1β concentrations were oriented in different directions. These dual effects occur partly through the modulation of mBDNF signaling.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156877"},"PeriodicalIF":3.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350706","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":"Are F2-isoprostanes a better marker of semen lipid peroxidation than MDA in reproductive pathologies with inflammatory basis?","authors":"Elena Moretti ,&nbsp;Cinzia Signorini ,&nbsp;Silvia Menchiari ,&nbsp;Laura Liguori ,&nbsp;Roberta Corsaro ,&nbsp;Laura Gambera ,&nbsp;Giulia Collodel","doi":"10.1016/j.cyto.2025.156889","DOIUrl":"10.1016/j.cyto.2025.156889","url":null,"abstract":"<div><div>Many male reproductive pathologies and a part of undiagnosed infertility share an oxidative stress (OS) etiology with high reactive oxygen species and cytokine concentrations. The lack of reliable biomarkers to quantify oxidative injury is a crucial problem in the field of male infertility. In this observational study, IL-1β and the OS markers malondialdehyde (MDA) and F₂-isoprostanes (F₂-IsoPs) were quantified in seminal plasma of 46 infertile patients with varicocele, genitourinary infections, idiopathic infertility, and 11 fertile men. Semen analysis was performed following WHO guidelines, IL-1β was determined by ELISA, MDA was quantified by HPLC, and F₂-IsoPs by GC/NICI-MS analysis. F₂-IsoPs were immunolocalized in spermatozoa of fertile and infertile subjects. Results indicated that F₂-IsoP, MDA, and IL-1β seminal levels positively correlated pairwise (<em>p</em> &lt; 0.001) and showed negative correlations with sperm parameters (p &lt; 0.001). Then, the studied population was grouped following the cause of infertility and the variables were compared between the different groups and a control sample. Seminal IL-1β, F₂-IsoPs, and MDA were significantly higher in varicocele (<em>p</em> &lt; 0.001, for MDA <em>p</em> &lt; 0.01) and genitourinary infections (p &lt; 0.001, for IL-1β p &lt; 0.01) groups than those observed in fertile subjects. F₂-IsoPs seemed to discriminate more accurately than MDA the different conditions, in particular idiopathic infertility. ROC curves demonstrated that the three analyzed indices were able to discriminate fertile and infertile patients. The immunofluorescence studies showed a low presence of F₂-IsoPs in spermatozoa of fertile men and an evident labeling in the tail, and cytoplasmic residues of spermatozoa from infertile patients. In conclusion, this data confirmed that F₂-IsoP level is a suitable marker of OS in seminal plasma, even more accurate than MDA and can be proposed for measuring OS in the clinical setting.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156889"},"PeriodicalIF":3.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372681","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":"Preparation and functional identification of various porcine cytokines","authors":"Shanshan Yang ,&nbsp;Qiuxia Cao ,&nbsp;Kexin Yan ,&nbsp;Chuanhong Wang ,&nbsp;Xu Song ,&nbsp;Xianyu Bian ,&nbsp;Sufen Li ,&nbsp;Zhenkong Cheng ,&nbsp;Xuehan Zhang ,&nbsp;Yi Wang ,&nbsp;Rongli Guo ,&nbsp;Xiaodu Wang ,&nbsp;Houhui Song ,&nbsp;Baochao Fan ,&nbsp;Bin Li","doi":"10.1016/j.cyto.2025.156880","DOIUrl":"10.1016/j.cyto.2025.156880","url":null,"abstract":"<div><div>The insufficiency of current Porcine Epidemic Diarrhea (PED) vaccines against highly pathogenic strains highlights the critical importance of enhancing mucosal immunity in the prevention and control of porcine enteric viral diseases. Due to limited research platforms, the understanding of the porcine mucosal immune system and its response mechanisms remains incomplete. This study employed prokaryotic expression and purification methods to obtain eight essential cytokines involved in mucosal immune responses (CD40L, IL-2, IL-6, TNF-α, IL-13, IL-17α, TGF-β, APRIL). By utilizing various cell models including porcine intestinal organoids, IPEC-J2, Vero-E6, porcine peripheral blood lymphocytes, and porcine Peyer's patch lymphocytes, the functions of these eight cytokines were identified through flow cytometry, immunoblotting, relative quantitative PCR, and CFSE proliferation assays. The results demonstrate that all eight purified proteins exhibit both protein activity and function. The purification of these molecules lays the groundwork for further exploration of the mucosal barrier of pigs and mucosal immune-related studies, as well as providing research tools for the prevention and control of enteric viral diseases in pigs.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156880"},"PeriodicalIF":3.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143343577","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":"IL-27 aggravates acute hepatic injury by promoting macrophage M1 polarization to induce Caspase-11 mediated Pyroptosis in vitro and in vivo","authors":"Lin Ye ,&nbsp;Liuyang Wang ,&nbsp;Gang Kuang ,&nbsp;Zhijiao Zhang ,&nbsp;Qiaozhi Peng ,&nbsp;Miao He ,&nbsp;Jing Fan","doi":"10.1016/j.cyto.2025.156881","DOIUrl":"10.1016/j.cyto.2025.156881","url":null,"abstract":"<div><h3>Objectives</h3><div>Our aim was to explore the IL-27 effect in sepsis (SP)-related acute hepatic injury (AHI) as well as its possible mechanism.</div></div><div><h3>Materials and methods</h3><div>Herein, we utilized both wild-type (WT) and IL-27 receptor (WSX-1)-deficient (IL-27R^−/−) mice alongside RAW264.7 cells. Our study established an SP-associated AHI model through the intraperitoneal injections of lipopolysaccharide (LPS) + D-galactosamine (D-G). For examining the IL-27 impact on AHI, mice serum and liver tissue samples were gathered. Inflammatory factor levels in the liver and serum were detected using ELISA and immunohistochemistry. Immunofluorescence and Western blot techniques were employed for the detection of protein expression associated with polarization and pyroptosis in the liver, including iNOS, ARG-1, caspase-11, RAGE, and GSDMD. To further verify the IL-27 effects on macrophage polarization and pyroptosis and explore possible mechanisms involved, we used LPS-triggered RAW264.7 macrophages to assess AMPK/SIRT1 expression after IL-27 intervention. This study utilized Compound C (CC) to block the AMPK/SIRT1 pathway. The inflammatory response level and protein expression related to macrophage polarization and pyroptosis were measured again to reveal IL-27 implication in AHI and determine whether its role is associated with the AMPK/SIRT1 pathway.</div></div><div><h3>Results</h3><div>The results revealed that IL-27 exacerbated systemic inflammation and liver damage in AHI mice by promoting M1 macrophage polarization, thereby increasing pro-inflammatory phenotype macrophages (M1). This further exacerbated the inflammatory response and pyroptosis <em>in vivo</em> and <em>in vitro</em>. Additionally, IL-27 down-regulated p-AMPK and SIRT1 protein expression while overexpressing macrophage inflammatory mediators including IL-1β/6 and TNFα. Furthermore, IL-27 promoted increased RAGE and caspase-11 protein expression, aggravating macrophage pyroptosis. Employing CC to block the AMPK pathway further aggravated M1 macrophage polarization and pyroptosis <em>in vitro</em> and <em>in vivo</em>, ultimately worsening liver injury.</div></div><div><h3>Conclusions</h3><div>Here, IL-27 aggravates AHI by promoting macrophage M1 polarization to induce caspase-11-mediated pyroptosis <em>in vitro</em> and <em>in vivo</em>, which may be linked to the AMPK/SIRT1 signaling pathway.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156881"},"PeriodicalIF":3.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143343574","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":"IL-17A, IL-23R, FCGR3A are associated with neuropsychiatric systemic lupus erythematosus susceptibility in pediatric patients with lupus nephritis","authors":"Chen Ye ,&nbsp;Lizhi Chen ,&nbsp;Lu Zhang ,&nbsp;Yifan Zheng ,&nbsp;Xiaohong Liu ,&nbsp;Zhijun Huang ,&nbsp;Kejing Tang ,&nbsp;Xiaoyun Jiang ,&nbsp;Pan Chen","doi":"10.1016/j.cyto.2025.156874","DOIUrl":"10.1016/j.cyto.2025.156874","url":null,"abstract":"<div><h3>Objective</h3><div>To comprehensively investigate the impact of candidate loci on the susceptibility to neuropsychiatric systemic lupus erythematosus (NPSLE) in a cohort of Chinese children with lupus nephritis (LN).</div></div><div><h3>Methods</h3><div>This case-control study included sixty-two patients. And the case group consisted of 12 LN patients appearing NPSLE, while the control group consisted of 50 LN patients. A total of fifty-four single nucleotide polymorphisms (SNPs) across twenty genes were genotyped using the Agena Bioscience MassArray iPLEX platform. The associations between susceptibility to NPSLE and candidate SNPs were assessed using SNPStats online software. We evaluated the influence of candidate SNPs on the risk of NPSLE through odds ratios (OR) and 95 % confidence intervals (CI). Additionally, linkage disequilibrium (LD) and coefficient (D′ and r²) for haplotypes and their frequencies were performed using the genetic statistical online software SHEsis.</div></div><div><h3>Results</h3><div>Three significant SNPs were identified: <em>IL17RA</em> rs2895332, <em>IL23R</em> rs10889677, and <em>FCGR3A</em> rs396991. <em>AA</em> genotype of <em>FCGR3A</em> rs396991, GG genotype of <em>IL17RA</em> rs2895332 and AA genotype of <em>IL23R</em> rs10889677 exhibited a decreased risk of NPSLE compared to CA and CC genotypes, GA and AA genotypes, and CA and CC genotypes (rs396991 AA vs. CA-CC, OR 5.00, 95 %CI 0.99–25.17, <em>P</em> = 0.029; rs2895332 GG vs. GA-AA, OR 7.83, 95 %CI 1.47–41.79, <em>P</em> = 0.017; rs10889677 AA vs. CA-CC, OR 4.50, 95 %CI 1.08–18.69, <em>P</em> = 0.027). Furthermore, the haplotype A-T-G (<em>STAT4</em> rs13426947, rs1551443 and rs3024866) appeared to confer protection against the development of NPSLE. The multivariate logistic regression analysis indicated that two specific SNPs were significantly associated with an increased risk of NPSLE: [<em>FCGR3A</em> rs396991 (OR = 6.444, 95 %CI = 1.1–37.736, <em>P</em> = 0.039), <em>IL17RA</em> rs2895332 (OR = 0.128, 95 %CI = 0.017–0.963, <em>P</em> = 0.046)]. Notably, the RegulomeDB score of them reached 1 f. Using HaploReg, these loci were in strong LD (r²&gt;0.8) with several SNPs.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that the polymorphisms <em>IL17RA</em> rs2895332, <em>IL23R</em> rs10889677, and <em>FCGR3A</em> rs396991 are significantly associated with the risk of NPSLE in childhood-onset LN.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156874"},"PeriodicalIF":3.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143131156","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}