Cytokine最新文献

{"title":"TNF-α/IL-1β/IL-1α/IL-12 inflammatory cytokine axes coupled with TLR1/TLR3/TLR5/MYD88 immune signaling pathway over-activation contribute to simultaneous carotid and coronary artery and occlusion in elderly patients","authors":"Wenhang Zhou ,&nbsp;Xia Li ,&nbsp;Hualan Zhou ,&nbsp;Youdong Hu ,&nbsp;Ying Chen ,&nbsp;Dianxuan Guo","doi":"10.1016/j.cyto.2024.156808","DOIUrl":"10.1016/j.cyto.2024.156808","url":null,"abstract":"<div><h3>Background</h3><div>It remains difficult to evaluate the risk factors for concomitant carotid artery as well as coronary artery diseases in elderly patients. The aim of this research was to determine the TNF-α/IL-1β/IL-1α/IL-12 axes-TLR1/TLR3/TLR5/MYD88 immune signaling pathway interactions in coexistent carotid artery occlusion and coronary artery occlusion in elderly patients.</div></div><div><h3>Methods</h3><div>Elderly patients, who underwent carotid ultrasonography and coronary computed tomography angiography, were consecutively included in this research. The analyzed groups consisted of those with coexistent carotid artery occlusion and coronary artery occlusion as well as healthy individuals were enrolled as control group. The circulating levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-1α (IL-1α), interleukin-12 (IL-12), toll-like receptor 1 (TLR1), toll-like receptor 3 (TLR3), toll-like receptor 5 (TLR5) and myeloid differentiation factor 88 (MYD88) were measured.</div></div><div><h3>Results</h3><div>The biomarkers (TNF-α, IL-1β, IL-1α, IL-12, TLR1, TLR3, TLR5 and MYD88) were significantly increased in carotid artery occlusion + left circumflex coronary artery occlusion group when compared with control group and carotid artery occlusion + right coronary artery occlusion group, respectively (<em>P</em> &lt; 0.001), and were further elevated in carotid artery occlusion + left anterior descending coronary artery occlusion group when compared to carotid artery occlusion + right coronary artery occlusion group and carotid artery occlusion + left circumflex coronary artery occlusion group, respectively (<em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>This research demonstrated that the TNF-α/IL-1β/IL-1α/IL-12 axes and TLR1/TLR3/TLR5/MYD88 immune signaling pathway implicated in the pathogenesis of carotid artery occlusion with coronary artery occlusion in elderly patients.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156808"},"PeriodicalIF":3.7,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142661849","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 relationship between 25-hydroxyvitamin D and markers of intestinal and systemic inflammation in undernourished and non-undernourished children, 6–59 months","authors":"Janet Adede Carboo,&nbsp;Linda Malan,&nbsp;Martani Lombard,&nbsp;Arista Nienaber,&nbsp;Robin Claire Dolman-Macleod","doi":"10.1016/j.cyto.2024.156807","DOIUrl":"10.1016/j.cyto.2024.156807","url":null,"abstract":"<div><h3>Background</h3><div>Elevated inflammation contributes to growth faltering in children. Vitamin D (vitD) suppresses pro-inflammatory and enhances anti-inflammatory molecule production, thus vitamin D deficiency (VDD) has been associated with heightened inflammation. In undernourished children, VDD and inflammation co-exist, however, little is known about their interaction.</div></div><div><h3>Objective</h3><div>This cross-sectional study aimed to investigate the association of serum 25-hydroxyvitamin D (25(OH)D) concentration with markers of inflammation in undernourished and non-undernourished children, as well as the effect of vitD supplementation on inflammatory markers in the children with low 25(OH)D in a nested before-and-after trial.</div></div><div><h3>Methods</h3><div>Serum 25(OH)D, IL-1β, IL-8, IL-10, TNF-α, CRP, AGP, IFABP, sCD14, IGF-1 and FGF-21 of 121 undernourished and 51 non-undernourished children aged 6–59 months were measured cross-sectionally. Children with serum 25(OH)D &lt; 30 ng/mL received 50,000 IU/week of vitD for three weeks.</div></div><div><h3>Results</h3><div>TNF-α and FGF-21 in the overall and undernourished group were higher in those with serum 25(OH)D &lt; 30 ng/mL compared to those with serum ≥ 30 ng/mL (p &lt; 0.05), while IFABP concentration was higher in the non-undernourished children with serum 25(OH)D &lt; 30 ng/mL (p = 0.047). Serum 25(OH)D was negatively associated with TNF-α in the overall group (β = −0.012, p = 0.034); and FGF-21 (β = −0.013, p = 0.023) in the undernourished group. After the supplementation trial, TNF-α was reduced by 55.9 % (p = 0.008) and 64.7 % (p = 0.017) in the overall and undernourished groups respectively, and AGP showed a trend of 41.6 % reduction (p = 0.099) in the overall group. IL-1β concentration increased post-supplementation in the overall (p = 0.011) and undernourished groups (p = 0.039).</div></div><div><h3>Conclusion</h3><div>Optimising vitD status may potentially be a strategy for reducing systemic and gut inflammation, and subsequently improving growth, particularly in undernourished children.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156807"},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646062","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":"Antibody isotyping and cytokine profiling in natural cases of Burkholderia mallei infection (glanders) in equines","authors":"Pooja ,&nbsp;Naintara Thapa ,&nbsp;Radha Rani ,&nbsp;Karuppusamy Shanmugasundaram ,&nbsp;Punit Jhandai ,&nbsp;Rakshita ,&nbsp;Tarun Kumar Bhattacharya ,&nbsp;Harisankar Singha","doi":"10.1016/j.cyto.2024.156799","DOIUrl":"10.1016/j.cyto.2024.156799","url":null,"abstract":"<div><h3>Objectives</h3><div>Immunological aspects of <em>B. mallei</em> infection were rarely studied in natural cases of equines. The present study was conducted to determine IgG, IgM, IgA and IgG (T) titre against recombinant Hcp1, TssA and TssB proteins and PilA-Hcp1-TssN-BipD and BpaB-BpaC- BMAA0553 chimeras and cytokine responses in glanders affected equine serum.</div></div><div><h3>Methods</h3><div>The study was conducted on serum samples collected from 151 glanders positive equines which include horses (n = 134), mules (n = 16), and donkeys (n = 01). The IgM, IgG, IgA and IgG (T) titre were determined against recombinant antigens by indirect ELISA and interleukin(IL)-1β, IL-17, IL-6, tumor necrosis factor alpha<!--> <!-->(TNF-α), monocyte chemoattractant protein 1 (MCP-1) and interferon gamma (IFN-γ) responses were measured by commercial ELISA kits.</div></div><div><h3>Results</h3><div>The study showed that glanders affected equines elicited strong antibody response against Hcp1, moderate responses against TssA and TssB, and weak responses against two chimeras. Among the cytokines, IL-1β, MCP-1, IL-17 and IL-6 concentration were significantly higher in glanders affected equine serum.</div></div><div><h3>Conclusion</h3><div>We found that IgG antibody titre was higher than IgM, IgG (T) and IgA isotypes and Hcp1 was most predominant antibody inducers in comparison to TssA, TssB, PilA-Hcp1-TssN-BipD and BpaB-BpaC-T2SS proteins. The elevated level of IL-1β, MCP-1, IL-17, IL-6, IFN-γ and TNF-α observed in this study support the important role of this cytokines for augmenting cellular defence by recruitment of macrophages, neutrophil and dendritic cells against <em>B. mallei</em> infection. Further studies should be conducted to determine memory cell responses in natural cases of equine glanders using recombinant <em>B. mallei</em> proteins for identifying well-characterized immuno-protective vaccine candidates.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156799"},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643602","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":"Risk factors associated with short-term mortality in patients with candidemia and the predictive value of serum cytokine level","authors":"Xueqing Fang ,&nbsp;Congling Su ,&nbsp;Yan Luo ,&nbsp;Kai Pan ,&nbsp;Jian Lin ,&nbsp;Youliang Song ,&nbsp;Yize Huang ,&nbsp;Xiaochun Hu ,&nbsp;Zhiyong Shen","doi":"10.1016/j.cyto.2024.156803","DOIUrl":"10.1016/j.cyto.2024.156803","url":null,"abstract":"<div><h3>Background</h3><div>Some pro-inflammatory and anti-inflammatory cytokines were significantly elevated in patients with candidemia patients, but no studies have included these cytokines in the analysis of risk factors for mortality of candidemia. This study aims to analyze the risk factors of short-term mortality of candidemia and the predictive value of serum cytokines.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed and compared the clinical features, risk factors and cytokine interleukin (IL)-6, interferon-γ (IFN-γ), IL-10 and IL-17 between survival group and death group in 53 patients with candidemia. Receiver operating of the characteristic curve (ROC) analysis was performed and figured up area under the curve (AUC), sensitivity and specificity values to assess the predictive power of independent factors associated with mortality.</div></div><div><h3>Results</h3><div>The overall in-hospital mortality rate of candidemia was 62.3 % (33/53), and the 30-day mortality rate was 52.8 % (28/53). The C. albicans accounting for 17.0 % (9/53), and the non-albicans Candida was 83.0 % (44/53). Serum IL-6 (p = 0.041, HR = 1.009), IFN-γ (p = 0.013, HR = 1.007, 95 %), procalcitonin (PCT) (p = 0.010, HR = 0.899) and Candida score (p = 0.033, HR = 1.659) were independent risk factors, while Initiation of targeted antifungal therapy within 48 h of positive blood cultures (BC) (P = 0.015, HR = 0.266) was a protective factor. The AUC of ROC for Candida score, serum IL-6, PCT, IFN-γ, and Initiation of targeted antifungal therapy within 48 h of positive BC showed 0.933, 0.841, 0.801, 0.732, 0.714, respectively. IL-6 and IFN-γ comprised good performing model for predicting 30-day and 90-day mortality, while IL-6 and IL-10 were the best combinations for predicting 90-day mortality.</div></div><div><h3>Conclusions</h3><div>Serum IL-6, IFN-γ, PCT, and Candida score can predict short-term mortality risk in patients with candidemia, while prompt and targeted antifungal treatment may reduce mortality. IL-6 could serve as a possible biomarker for predicting short-term mortality of candidemia and its combination with IL-10 or IFN-γ may further improve the predictive value.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156803"},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637898","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 multifunctional role of IFN-γ in Galleria mellonella (Lepidoptera) immunocompetent cells","authors":"Agata Kaczmarek,&nbsp;Anna Katarzyna Wrońska,&nbsp;Justyna Sobich,&nbsp;Mieczysława Irena Boguś","doi":"10.1016/j.cyto.2024.156804","DOIUrl":"10.1016/j.cyto.2024.156804","url":null,"abstract":"<div><div>Cytokines are highly conserved between mammals and insects. The present study examines the multiple effects of interferon-gamma (IFN-γ) application on the immunological defence mechanisms of <em>Galleria mellonella</em> larvae, invertebrates which are gaining popularity as a replacement for mammalian research models in immunological studies. <em>G. mellonella</em> hemolymph is known to contain an IFN-γ homolog that shares 33 % similarity with its mammalian analogue, and its level in insect hemocytes increases during exposition to entomopathogenic fungus <em>Conidiobolus coronatus</em>. The present research examines the impact of IFN-γ on larval development, the effectiveness of fungal infection, and the morphology and physiology of wax moth immunocompetent cells. Treatment with IFN-γ enhanced wound healing, chemotaxis activity and hemocyte impedance, while reducing hemocyte phagocytosis and oxidative stress in cultured immunocompetent cells; it also appears to increase the levels of Jak-2- and NF-κB-like molecules in hemocytes. Our findings suggest that IFN-γ demonstrated considerable similarity between mammals and humans, thus further demonstrating the evolutionary conservatism of cytokines.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156804"},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637899","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":"Hypercapnia promotes NLRP3 inflammasome activation in microglia by activating P2X7R after lipopolysaccharide-induced activation of the TLR4/NF-κB signaling pathway","authors":"Hongguang Ding ,&nbsp;Shiying Zhang ,&nbsp;Zhuo Li ,&nbsp;Juhao Zeng ,&nbsp;Hongke Zeng","doi":"10.1016/j.cyto.2024.156806","DOIUrl":"10.1016/j.cyto.2024.156806","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis is an uncontrolled inflammatory response to infection and is closely associated with the occurrence of acute respiratory distress syndrome (ARDS). Low tidal volume lung ventilation and permissive hypercapnia is a recognized therapy for ARDS. However, whether permissive hypercapnia aggravates sepsis-associated encephalopathy (SAE) remains unclear. The present study investigated whether hypercapnia contributed to the development of SAE through the purinergic 2X7 receptor (P2X7R) by activating the Nod-like receptor protein 3 (NLRP3) inflammasome in sepsis.</div></div><div><h3>Methods</h3><div>The SAE model was established by intracranial injection of lipopolysaccharide (LPS) (1 μg/ml, 5 μl) in C57BL/6 mice. Hypercapnia was induced by mechanical ventilation with a high concentration of CO₂ (5 % CO₂, 21 % O₂ and 74 % N₂) <em>in vivo</em>. Toll-like receptor 4 (TLR4) and P2X7R knockout (KO) mice were employed in the study, while <em>in vitro</em>, BV2 microglial cells were treated with LPS or a high concentration of CO₂ (15 % CO₂ + 20 % O₂). Immunofluorescence and western blot analysis were used to assess the expression levels of TLR4, NF-κB, phosphorylated (p)-NF-κB, P2X7R, pro-caspase-1, caspase-1, pro-IL-1β, IL-1β, pro-IL-18 and IL-18. ATP levels in the cell culture medium were detected by fluorometric assay.</div></div><div><h3>Result</h3><div>The results revealed that, compared with the sham group, the expression levels of TLR4, p-NF-κB, pro-IL-1β, pro-IL-18 and NLRP3 were significantly upregulated in the LPS and LPS + hypercapnia groups, but not in the hypercapnia group. Although the expression levels of caspase-1, IL-1β and IL-18 were increased slightly in the LPS group, their upregulation was more pronounced in the LPS + hypercapnia group, and it was suppressed when TLR4 was knocked out. Furthermore, P2X7R expression and ATP levels in the cell culture medium remained unchanged in the LPS group compared with the sham group but were remarkably increased both in the hypercapnia and LPS + hypercapnia groups. Additionally, P2X7R KO restrained the caspase-1, IL-1β and IL-18 increased induced by LPS injected intracranially and hypercapnia.</div></div><div><h3>Conclusions</h3><div>In conclusion, LPS induced the priming step of NLRP3 inflammasome activation, but had little effect on the activation step, while hypercapnia played an important role in the activation step through P2X7R, depending on the priming step stimulated by LPS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156806"},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643603","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":"Exploring the innate immune response in polycystic liver disease","authors":"Renée Duijzer ,&nbsp;Daisy Dalloyaux ,&nbsp;Melissa M. Boerrigter ,&nbsp;Heidi Lemmers ,&nbsp;Helga Dijkstra ,&nbsp;Liesbeth van Emst ,&nbsp;René H.M. te Morsche ,&nbsp;Martin Jaeger ,&nbsp;Leo A.B. Joosten ,&nbsp;Joost P.H. Drenth","doi":"10.1016/j.cyto.2024.156800","DOIUrl":"10.1016/j.cyto.2024.156800","url":null,"abstract":"<div><h3>Rationale</h3><div>The role of the innate immune system in polycystic liver disease (PLD) has been underexplored despite its potential importance in disease progression. This study explores the innate immune response in PLD patients by analyzing cytokine production of peripheral blood mononuclear cells (PBMCs) in response to various pathogens compared to healthy controls.</div></div><div><h3>Methods</h3><div>Samples were collected from patients with ADPLD or ADPKD and PLD. PBMCs were isolated and stimulated with LPS (1 ng), LPS (10 ng), <em>E. coli</em>, <em>K. pneumoniae</em>, <em>S. aureus</em>, and <em>C. albicans</em>. ELISA was used to measure TNF, IL-1β, IL-1Ra, IL-6, and IL-8 concentrations after 24 hours, and IL-17, IL-22, and IFNγ concentrations after 7 days. Control samples were matched for age and gender.</div></div><div><h3>Results</h3><div>104 patients and 12 controls were included. PLD patients showed consistent increased IL-6 concentrations compared to controls. Other cytokine levels varied per stimulus. Controls showed higher IL-8 and TNF concentrations in response to Gram-negative bacteria, while PLD patients showed higher IL-1β and IL-1Ra levels in response to <em>S. aureus</em> and <em>C. albicans</em>. No clear differences were found in IL-17, IL-22, and IFN-γ concentrations after 7 days. These observed differences were independent of demographic and clinical parameters.</div></div><div><h3>Conclusion</h3><div>Compared to healthy controls, the PLD patients innate immune system shows an altered response when stimulated by various pathogens. These findings underscore the importance of further investigation into the underlying mechanisms as this might help our understanding disease progression and be a potential target for new therapies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156800"},"PeriodicalIF":3.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610820","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":"The cGAS-STING pathway as a novel therapeutic strategy for pancreatic diseases","authors":"Zhengda Pei ,&nbsp;Mengxiang Tian","doi":"10.1016/j.cyto.2024.156801","DOIUrl":"10.1016/j.cyto.2024.156801","url":null,"abstract":"<div><div>The Cyclic GMP-AMP synthase (cGAS)-Stimulator of interferon genes <span><span>[1]</span></span> signaling pathway has emerged as a pivotal immune response mechanism, activating immune defenses upon detection of both exogenous and endogenous DNA within cells. Its activation is intricately linked to various diseases and inflammatory processes, spanning autoimmune disorders, infectious ailments, and malignancies. Among pancreatic diseases, encompassing acute pancreatitis, chronic pancreatitis, and pancreatic cancer, current clinical treatment efficacy remains suboptimal. Here, we elucidate the molecular intricacies of the cGAS-STING signaling pathway and delineate its therapeutic potential in acute pancreatitis, chronic pancreatitis, and pancreatic cancer. Additionally, we offer an overview of recent advancements in STING agonists and antagonists, assessing their therapeutic potential in pancreatic-related disorders. In summary, by exploring the multifaceted roles of the cGAS-STING signaling pathway and its implications in pancreatic diseases, we aim to shed light on potential avenues for therapeutic intervention and management in these challenging clinical contexts.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156801"},"PeriodicalIF":3.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610821","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":"Soybean lectin-triggered IL-6 secretion induces autophagy to kill intracellular mycobacteria through P2RX7 dependent activation of the JAK2/STAT3/Mcl-1 pathway","authors":"Abtar Mishra ,&nbsp;Ashish Kumar ,&nbsp;Lincoln Naik ,&nbsp;Salina Patel ,&nbsp;Mousumi Das ,&nbsp;Assirbad Behura ,&nbsp;Dev Kiran Nayak ,&nbsp;Amit Mishra ,&nbsp;Sujit K. Bhutia ,&nbsp;Ramandeep Singh ,&nbsp;Rohan Dhiman","doi":"10.1016/j.cyto.2023.156366","DOIUrl":"10.1016/j.cyto.2023.156366","url":null,"abstract":"<div><p>Cytokine therapy and cytokine-mediated autophagy have been used as prominent host-directed therapy (HDT) approaches to restrain <em>M. tb</em> growth in the host cell. In the present study, we have dissected the anti-tubercular activity of Soybean lectin (SBL) through cytokine-mediated autophagy induction in differentiated THP-1 (dTHP-1) cells. A significant increase in IL-6 expression was observed in both uninfected and mycobacteria infected dTHP-1 cells through the P2RX7 mediated pathway via PI3K/Akt/CREB-dependent signalling after SBL treatment. Inhibition of IL-6 level using IL-6 neutralizing antibody or associated signalling significantly enhanced the mycobacterial load in SBL-treated dTHP-1 cells. Further, autocrine signalling of IL-6 through its receptor-induced Mcl-1 expression activated autophagy via JAK2/STAT3 pathway, and inhibition of this pathway affected autophagy. Finally, blocking the IL-6-regulated autophagy through NSC 33994 (a JAK2 inhibitor) or S63845 (an Mcl-1 inhibitor) led to a notable increase in intracellular mycobacterial growth in SBL-treated cells. Taken together, these results indicate that SBL interacts with P2RX7 to regulate PI3K/Akt/CREB network to release IL-6 in dTHP-1 cells. The released IL-6, in turn, activates the JAK2/STAT3/Mcl-1 pathway upon interaction with IL-6Rα to modulate autophagy that ultimately controls mycobacterial growth in macrophages.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"171 ","pages":"Article 156366"},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261725","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":"Quercetin protects against Aspergillus fumigatus keratitis by reducing fungal load and inhibiting TLR-4 induced inflammatory response","authors":"Junjie Luan ,&nbsp;Yunan Zhu ,&nbsp;Jing Lin ,&nbsp;Yingxue Zhang ,&nbsp;Qiang Xu ,&nbsp;Lu Zhan ,&nbsp;Xue Tian ,&nbsp;Guiqiu Zhao ,&nbsp;Xudong Peng","doi":"10.1016/j.cyto.2023.156356","DOIUrl":"10.1016/j.cyto.2023.156356","url":null,"abstract":"<div><h3>Purpose</h3><p>To investigate the antifungal and anti-inflammatory effects of quercetin in <em>Aspergillus fumigatus</em> (<em>A. fumigatus</em>) keratitis.</p></div><div><h3>Methods</h3><p>Draize eye test was performed in mice to evaluate the toxicity of quercetin, and the antifungal effects on <em>A. fumigatus</em> were assessed via scanning electron microscopy (SEM), propidium iodide uptake, and adherence assay. In fungal keratitis (FK) mouse models, immunostaining was performed for investigating toll-like receptor 4 (TLR-4) expression and macrophage infiltration. Real-time PCR, ELISA, and Western blot were used to evaluate the expression of pro-inflammatory factors IL-1β, TNF-α, and IL-6 in infected RAW264.7 cells. Cells were also treated with TLR-4 siRNA or agonist CRX-527 to investigate mechanisms underlying the anti-inflammatory activity of quercetin.</p></div><div><h3>Results</h3><p>Quercetin at 32 μM was non-toxic to corneal epithelial and significantly inhibited <em>A. fumigatus</em> growth and adhesion, and also altered the structure and reduced the number of mycelia. Quercetin significantly reduced macrophage infiltration in the mouse cornea, and attenuated the expression of TLR-4 in the corneal epithelium and stroma of mice with keratitis caused by <em>A. fumigatus</em>. In RAW264.7 cells infected by <em>A. fumigatus</em>, quercetin downregulated TLR-4 along with pro-inflammatory factors IL-1β, TNF-α, and IL-6. RAW cells with TLR-4 knockdown had reduced expression of factors after <em>A. fumigatus</em> infection, which was decreased even further with quercetin treatment. In contrast, cells with CRX-527 had elevated inflammatory factors compared to control, which was significantly attenuated in the presence of quercetin.</p></div><div><h3>Conclusion</h3><p>Quercetin plays a protective role in mouse <em>A. fumigatus</em> keratitis by inhibiting fungal load, disrupting hyphae structure, macrophage infiltration, and suppressing inflammation response in macrophages via TLR-4 mediated signaling pathway.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"171 ","pages":"Article 156356"},"PeriodicalIF":3.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10237825","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}