Cytokine最新文献

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

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

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

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

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

{"title":"In vivo overexpression of the avian interleukin-17 in a necrotic enteritis disease model modulates the expression of antimicrobial peptides in the small intestine of broilers","authors":"Nitish Boodhoo,&nbsp;Myles St-Denis,&nbsp;Jiayu Zheng,&nbsp;Bhavya Gupta,&nbsp;Shayan Sharif","doi":"10.1016/j.cyto.2024.156749","DOIUrl":"10.1016/j.cyto.2024.156749","url":null,"abstract":"<div><p>In humans and mice, the induction of interleukin (IL)-17 expression enhances epithelial barrier integrity through the secretion of antimicrobial peptides (AMP), thereby improving antibacterial defense. However, it is unclear whether IL-17 has similar antibacterial effects in chickens by modulating the expression of AMPs, such as avian beta-defensins (also known as gallinacins) and cathelicidins. This study evaluated the in vivo effects of inoculating 20-day-old broiler chickens with two doses of a plasmid encoding chicken IL-17 (pCDNA3.1/rchIL-17-V5-HIS TOPO plasmid [pCDNA3.1-IL-17]; 5 or 10 μg/bird). On day 23 of age, all broilers, except those in the negative control group, were orally challenged with a virulent <em>Clostridium perfringens</em> strain for three days. To investigate IL-17-mediated effects against <em>C. perfringens</em> infection, the expression of avian beta-defensin 1 (avBD1), avBD2, avBD4, avBD6, cathelicidins, and inducible nitric oxide synthase (iNOS) genes were quantified, and gross necrotic enteritis (NE) lesion scores were assessed in the small intestine. The results showed that broilers receiving the higher dose of pCDNA3.1-IL-17 (10 μg) had significantly lower NE lesion scores compared to those receiving the lower dose (5 μg), the vector control, and the positive control groups. Furthermore, the expression of all avian beta-defensins and cathelicidin genes was detectable across all groups, regardless of treatment and time points. IL-17 treatment led to significantly higher expression of avBD1, avBD2, avBD4, avBD6, cathelicidin, and iNOS in the duodenum, jejunum, and ileum compared to control chickens. In <em>C. perfringens</em>-infected chickens, the expression of avBD1, avBD2, avBD4, cathelicidin, and iNOS in the ileum was significantly higher than in control chickens. Pre-treatment with the higher dose of pCDNA3.1-IL-17 (10 μg) in infected chickens was associated with reduced NE lesion severity and increased expression of avBD1, avBD2, cathelicidin, and iNOS in the ileum, but not avBD4 and avBD6. These findings provide new insights into the potential effect of IL-17 and reduction in NE lesion severity by modulating AMP expression which may be involved in mediating protective immunity against intestinal infection with <em>C. perfringens</em>.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156749"},"PeriodicalIF":3.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043466624002527/pdfft?md5=66c2a5873627ffcee092ea240e6f0d54&pid=1-s2.0-S1043466624002527-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136633","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 role of M1 (CD11c) and M2 (CD163) interplay in the pathogenesis of oral submucous fibrosis and its malignant transformation: An immunohistochemical analysis","authors":"Nishreen M. Parekh,&nbsp;Rajiv S. Desai,&nbsp;Shivani P. Bansal,&nbsp;Pankaj M. Shirsat,&nbsp;Pooja S. Prasad","doi":"10.1016/j.cyto.2024.156742","DOIUrl":"10.1016/j.cyto.2024.156742","url":null,"abstract":"<div><h3>Objectives</h3><p>The M1/M2 macrophage framework is crucial in organ fibrosis and its progression to malignancy. This study investigated the possible role of M1/M2 macrophage interplay in the pathogenesis of oral submucous fibrosis (OSF) and its malignant transformation by analysing immunohistochemical expression of CD11c (M1) and CD163 (M2) markers.</p></div><div><h3>Methods</h3><p>Immunohistochemistry was performed using primary antibodies against CD11c and CD163 on ten formalin-fixed paraffin-embedded tissue blocks for each group: (i) Stage 1 OSF, (ii) Stage 2 OSF, (iii) Stage 3 OSF, (iv) Stage 4 OSF, (v) well-differentiated squamous cell carcinoma (WDSCC) with OSF, and (vi) WDSCC without OSF. Ten cases of healthy buccal mucosa (NOM) served as controls.</p></div><div><h3>Results</h3><p>Epithelial quick scores of M1 (CD11c) in NOM, Stages 1–4 OSF, and WDSCC with and without OSF were 0, 1.8, 2.9, 0.4, 0, 0, and 0, while connective tissue scores were 0, 3.2, 4.3, 2.7, 0.5, 1.2, and 2.4, respectively. Epithelial scores for M2 (CD163) were 0, 0.8, 0.8, 2.1, 0.6, 0.8, and 0.2, and connective tissue scores were 0, 1.8, 2.6, 3.9, 2.2, 5, and 4.4, respectively. Stages 3 and 4 OSF, WDSCC with and without OSF exhibited higher M2/M1 ratios compared to NOM and Stages 1–2 OSF.</p></div><div><h3>Conclusion</h3><p>The interaction between M1 (CD11c) and M2 (CD163) macrophages, leading to M2 polarisation, plays a crucial role in the pathogenesis of OSF and its potential malignant transformation.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156742"},"PeriodicalIF":3.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099365","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 effects of Staphylococcus aureus protein a (SpA) on the expression of inflammatory cytokines in autoimmune patients and their probable immune response modulation mechanisms","authors":"Garshasb Rigi ,&nbsp;Gholamali Kardar ,&nbsp;Abbas Hajizade ,&nbsp;Javad Zamani ,&nbsp;Gholamreza Ahmadian","doi":"10.1016/j.cyto.2024.156745","DOIUrl":"10.1016/j.cyto.2024.156745","url":null,"abstract":"<div><p>The recombinant Staphylococcal protein A (SpA) is widely used in biotechnology to purify polyclonal and monoclonal IgG antibodies. At very low concentrations, the highly-purified form of the protein A can down-regulate the activation of human B-lymphocytes and macrophages which are the key cells in determining autoimmune diseases. In the present study, the efficiency of three different forms of protein A, including native full-length SpA, the recombinant full-length SpA, and a recombinant truncated form of SpA on the reduction of 4 inflammatory cytokines, including IL-8, IL-1β, TNF-α, and IL-6 by peripheral blood mononuclear cell (PBMCs) were studied and compared to an anti-rheumatoid arthritis commercial drug, Enbrel. The recombinant proteins were expressed in <em>E. coli</em> and the native form of SpA was commercially provided. PBMCs were obtained from adult patients with active rheumatoid arthritis (RA) and healthy control donors. Then, the effect of different doses of the three pure forms of SpA in comparison with Enbrel was investigated by analyzing the expression of selected cytokines using ELISA. The results showed that the truncated form of recombinant SpA significantly reduced the expression of cytokines more effectively than the other full-length formulations as well as the commercial drug Enbrel. <em>In silico</em> analysis shows that in the truncated protein, as the radius of gyration increases, the structure of IgG-binding domains become more open and more exposed to IgG. To summarize, our findings indicate that the truncated form of protein A is the most efficient form of SpA as it significantly decreases the secretion of evaluated cytokines from PBMCs in vitro<em>.</em></p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156745"},"PeriodicalIF":3.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099366","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":"Morphine induces inflammatory responses via both TLR4 and cGAS-STING signaling pathways","authors":"Fei Xie ,&nbsp;Yoshinori Kitagawa ,&nbsp;Hiroki Ogata ,&nbsp;Shingo Yasuhara ,&nbsp;Zerong You ,&nbsp;J.A. Jeevendra Martyn","doi":"10.1016/j.cyto.2024.156737","DOIUrl":"10.1016/j.cyto.2024.156737","url":null,"abstract":"<div><h3>Background</h3><p>Opioid activation of the microglia or macrophage Toll-like receptor 4 (TLR4) and associated inflammatory cytokine release are implicated in opioid-induced hyperalgesia and tolerance. The cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS-STING) signaling pathway, activated by double-stranded DNA including mitochondrial DNA (mtDNA), has emerged as another key mediator of inflammatory responses. This study tested the hypothesis that morphine induces immune inflammatory responses in microglia and macrophages involving TLR4 and cGAS-STING pathway.</p></div><div><h3>Methods</h3><p>BV2 microglia and Raw 264.7 (Raw) macrophage cells were exposed to morphine with and without a STING inhibitor (C176) for 6 h or TLR 4 inhibitor (TAK242) for 24 h. Western blotting and RT-qPCR analyses assessed TLR4, cGAS, STING, nuclear factor-kappa B (NF-κB), and pro-inflammatory cytokine expression. Morphine-induced mitochondria dysfunction was quantified by reactive oxygen species (ROS) release using MitoSOX, mtDNA release by immunofluorescence, and RT-qPCR. Polarization of BV2 and Raw cells was assessed by inducible nitric oxide (iNOS) and CD86 expression. The role of mtDNA on morphine-related inflammation was investigated by mtDNA depletion of the cells with ethidium bromide (EtBr) or cell transfection of mtDNA extracted from morphine-treated cells.</p></div><div><h3>Results</h3><p>Morphine significantly increased the expression of TLR4, cGAS, STING, p65 NF-κB, and cytokines (IL-6 and TNF-α) in BV2 and Raw cells. Morphine-induced mitochondrial dysfunction by increased ROS and mtDNA release; the increased iNOS and CD86 evidenced inflammatory M1-like phenotype polarization. TLR4 and STING inhibitors reduced morphine-induced cytokine release in both cell types. The transfection of mtDNA activated inflammatory signaling proteins, cytokine release, and polarization. Conversely, mtDNA depletion led to the reversal of these effects.</p></div><div><h3>Conclusion</h3><p>Morphine activates the cGAS-STING pathway in macrophage cell types. Inhibition of the STING pathway can be an additional method to overcome immune cell inflammation-related morphine tolerance and opioid-induced hyperalgesia.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156737"},"PeriodicalIF":3.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099364","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":"Case-control study of IL23R rs76418789 polymorphism, smoking, and ulcerative colitis in Japan","authors":"Yoshihiro Miyake ,&nbsp;Keiko Tanaka ,&nbsp;Chisato Nagata ,&nbsp;Shinya Furukawa ,&nbsp;Akira Andoh ,&nbsp;Tetsuji Yokoyama ,&nbsp;Naoki Yoshimura ,&nbsp;Kenichiro Mori ,&nbsp;Tomoyuki Ninomiya ,&nbsp;Yasunori Yamamoto ,&nbsp;Eiji Takeshita ,&nbsp;Yoshio Ikeda ,&nbsp;Mitsuru Saito ,&nbsp;Katsuhisa Ohashi ,&nbsp;Hirotsugu Imaeda ,&nbsp;Kazuki Kakimoto ,&nbsp;Kazuhide Higuchi ,&nbsp;Hiroaki Nunoi ,&nbsp;Yuji Mizukami ,&nbsp;Seiyuu Suzuki ,&nbsp;Yoichi Hiasa","doi":"10.1016/j.cyto.2024.156743","DOIUrl":"10.1016/j.cyto.2024.156743","url":null,"abstract":"<div><h3>Background</h3><p>Interleukin (IL)-23 is involved in the pathogenesis of ulcerative colitis (UC). A genome-wide significant association between <em>IL23R</em> p.G149R (rs76418789) and UC was previously identified in Japan and Korea. This case-control study aims to examine this association within the Japanese population.</p></div><div><h3>Methods</h3><p>The study included 384 cases diagnosed with UC within the past 4 years and 661 control subjects. Adjustment was made for sex, age, and smoking.</p></div><div><h3>Results</h3><p>The frequency of the AA genotype of rs76418789 was 0.0 % in cases and 0.5 % in control subjects. In comparison to study subjects with the GG genotype of rs76418789, those with the GA or AA genotype had a significantly reduced risk of UC, with an adjusted odds ratio of 0.67 (95 % confidence interval: 0.44–0.999). A significant multiplicative interaction was observed between rs76418789 and having ever smoked influencing UC (<em>p</em> for interaction = 0.03). A significant positive association was found between having ever smoked and UC in individuals with at least one A allele, while no such positive relationship was observed in those with the GG genotype.</p></div><div><h3>Conclusion</h3><p><em>IL23R</em> SNP rs76418789 showed a significant association with UC. This study provides new evidence regarding the interaction between rs76418789 and smoking in relation to UC.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156743"},"PeriodicalIF":3.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099424","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}