{"title":"Role of Interleukin 1 Receptor 2 in Kidney Disease.","authors":"Huiyue Hu, Aihua Wu, Xiaodie Mu, Hua Zhou","doi":"10.1089/jir.2023.0172","DOIUrl":"10.1089/jir.2023.0172","url":null,"abstract":"<p><p>The interleukin 1 (IL-1) family plays a significant role in the innate immune response. IL-1 receptor 2 (IL-1R2) is the decoy receptor of IL-1. It is a negative regulator that can be subdivided into membrane-bound and soluble types. IL-1R2 plays a role in the IL-1 family mainly through the following mechanisms: formation of inactive signaling complexes upon binding to the receptor auxiliary protein and inhibition of ligand IL-1 maturation. This review covers the roles of IL-1R2 in kidney disorders. Chronic kidney disease, acute kidney injury, lupus nephritis, IgA nephropathy, renal clear cell carcinoma, rhabdoid tumor of kidney, kidney transplantation, and kidney infection were all shown to have abnormal IL-1R2 expression. IL-1R2 may be a potential marker and a promising therapeutic target for kidney disease.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"170-177"},"PeriodicalIF":1.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ponatinib and STAT5 Inhibitor Pimozide Combined Synergistic Treatment Applications Potentially Overcome Drug Resistance via Regulating the Cytokine Expressional Network in Chronic Myeloid Leukemia Cells.","authors":"Burcin Tezcanli Kaymaz, Nurcan Gumus, Besne Celik, İlayda Alcitepe, Cigir Biray Avci, Cagdas Aktan","doi":"10.1089/jir.2023.0170","DOIUrl":"10.1089/jir.2023.0170","url":null,"abstract":"<p><p>Chronic myeloid leukemia (CML) is a clonal myeloproliferative hematological disease characterized by the chimeric breakpoint-cluster region/Abelson kinase1 (BCR::ABL1) oncoprotein; playing a pivotal role in CML molecular pathology, diagnosis, treatment, and possible resistance arising from the success and tolerance of tyrosine kinase inhibitor (TKI)-based therapy. The transcription factor STAT5 constitutive signaling, which is influenced by the cytokine signaling network, triggers BCR::ABL1-based CML pathogenesis and is also relevant to acquired TKI resistance. The unsuccessful therapeutic approaches targeting BCR::ABL1, in particular third-line therapy with ponatinib, still need to be further developed with alternative combination strategies to overcome drug resistance. As treatment with the STAT5 inhibitor pimozide in combination with ponatinib resulted in an efficient and synergistic therapeutic approach in TKI-resistant CML cells, this study focused on identifying the underlying amplification of ponatinib response mechanisms by determining different cytokine expression profiles in parental and ponatinib-resistant CML cells, <i>in vitro</i>. The results showed that expression of interleukin <i>(IL) 1B</i>, <i>IL9</i>, and <i>IL12A-B</i> was increased by 2-fold, while <i>IL18</i> was downregulated by 2-fold in the ponatinib-resistant cells compared to sensitive ones. Importantly, ponatinib treatment upregulated the expression of 21 of the 23 interferon and <i>IL</i> genes in the ponatinib-resistant cells, while treatment with pimozide or a combination dose resulted in a reduction in the expression of 19 different cytokine genes, such as for example, inflammatory cytokines, <i>IL1A-B</i> and <i>IL6</i> or cytokine genes associated with supporting tumor progression, leukemia stem cell growth or poor survival, such as <i>IL3</i>, <i>IL8</i>, <i>IL9</i>, <i>IL10</i>, <i>IL12</i>, or <i>IL15</i>. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis results showed that the genes were mainly enriched in the regulation of receptor signaling through the Janus kinase/signal transducer and activator of transcription pathway, cytokine-cytokine receptor interaction, and hematopoietic cell lineage. Protein-protein interaction analysis showed that <i>IL2</i>, <i>IL6</i>, <i>IL15</i>, <i>IFNG</i>, and others appeared in the top lists of pathways, indicating their high centrality and importance in the network. Therefore, pimozide could be a promising agent to support TKI therapies in ponatinib resistance. This research would help to clarify the role of cytokines in ponatinib resistance and advance the development of new therapeutics to utilize the STAT5 inhibitor pimozide in combination with TKIs.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"44 4","pages":"178-189"},"PeriodicalIF":1.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interleukin-12: Structure, Function, and Its Impact in Colorectal Cancer.","authors":"Ziwei Zhu, Qian Peng, Xingmei Duan, Jie Li","doi":"10.1089/jir.2023.0190","DOIUrl":"10.1089/jir.2023.0190","url":null,"abstract":"<p><p>Interleukin 12 (IL-12) is a heterodimer consisting of 2 subunits, p35 and p40, with unique associations and interacting functions with its family members. IL-12 is one of the most important cytokines regulating the immune system response and is integral to adaptive immunity. IL-12 has shown marked therapeutic potential in a variety of tumor types. This review therefore summarizes the characteristics of IL-12 and its application in tumor treatment, focusing on its antitumor effects in colorectal cancer (CRC) and potential radiosensitization mechanisms. We aim to provide a current reference for IL-12 and other potential CRC treatment strategies.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"158-169"},"PeriodicalIF":1.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hale Radi, Elaheh Ferdosi-Shahandashti, Gholam Ali Kardar, Nasim Hafezi
{"title":"An Updated Review of Interleukin-2 Therapy in Cancer and Autoimmune Diseases.","authors":"Hale Radi, Elaheh Ferdosi-Shahandashti, Gholam Ali Kardar, Nasim Hafezi","doi":"10.1089/jir.2023.0178","DOIUrl":"10.1089/jir.2023.0178","url":null,"abstract":"<p><p>Interleukin-2 (IL-2) is a cytokine that acts in dual and paradoxical ways in the immunotherapy of cancers and autoimmune diseases. Numerous clinical trial studies have shown that the use of different doses of this cytokine in various autoimmune diseases, transplantations, and cancers has resulted in therapeutic success. However, side effects of varying severity have been observed in patients. In recent years, to prevent these side effects, IL-2 has been engineered to bind more specifically to its receptors on the cell surface, decreasing IL-2 toxicities in patients. In this review article, we focus on some recent clinical trial studies and analyze them to determine the appropriate dose of IL-2 drug with the least toxicities. In addition, we discuss the engineering performed on IL-2, which shows that engineered IL-2 increases the specificity function of IL-2 and decreases its adverse effects.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"143-157"},"PeriodicalIF":1.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sixun Zhong, Yan Zhang, Xiaomin Lu, Vafa Meftahpour
{"title":"The Therapeutic Potential of Cytokine-Induced Killer in Patients with Cancer.","authors":"Sixun Zhong, Yan Zhang, Xiaomin Lu, Vafa Meftahpour","doi":"10.1089/jir.2023.0180","DOIUrl":"10.1089/jir.2023.0180","url":null,"abstract":"<p><p>Despite the promising results of immunotherapy, further experiments need to be considered because of several factors ranging from physical barriers to off-tumor adverse effects. It is surprising that adoptive cellular immunotherapy, particularly dendritic cell and cytokine-induced killer (DC-CIK) therapy, is far less emphasized in the treatment of cancer diseases. DC-CIK therapy in cancer patients presents auspicious results with low or no side effects, which should not be overlooked. More interestingly, almost all DC-CIK clinical trials are ongoing in China that highlight the limitations of therapeutic strategies and require large-scale research. To date, it is advisable to consider combination therapy with chemotherapy since it has shown promising outcomes with higher efficacy. In this article, the efficacy of DC-CIK therapy in patients with cancer is summarized by underscoring the lack of experiments on soft cancers on an unprecedented scale. In brief, DC-CIK therapy is a safe and effective therapeutic agent for malignant and nonmalignant diseases that enhances short-term and long-term effects.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"44 3","pages":"99-110"},"PeriodicalIF":1.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingxing Yang, Guowei Xu, Jingyan Zhang, Zhiting Guo, Chao Liang, Yajun Li, Lei Wang, Yuxia Zhou, Yi Ru, Jianxi Li, Xuezhi Wang, Yan Sun
{"title":"Correlation Between MicroRNA by Extracellular Vesicle Mediated and Antiviral Effects of Interferon Omega in Feline Peripheral Blood.","authors":"Mingxing Yang, Guowei Xu, Jingyan Zhang, Zhiting Guo, Chao Liang, Yajun Li, Lei Wang, Yuxia Zhou, Yi Ru, Jianxi Li, Xuezhi Wang, Yan Sun","doi":"10.1089/jir.2023.0174","DOIUrl":"10.1089/jir.2023.0174","url":null,"abstract":"<p><p>Feline interferon omega (IFN-ω) has been proven to have high antiviral activity; however, its in-depth antiviral effects remain unknown. Extracellular vesicles (EVs) have been demonstrated to participate in the regulation of the immune response pathway for the body through various active substances, especially through the microRNA (miRNA) carried by them. In this study, we isolated EVs from feline peripheral blood by differential centrifugation, and further found that the content of IFN-ω in EVs increased continuously within 24 h after IFN-ω treatment, and a large number of miRNAs were significantly downregulated in EVs within 12 h after IFN-ω treatment. These significantly differentially expressed miRNAs were important for regulating changes in antiviral cytokines. This study reveals for the first time the correlation between EVs-mediated miRNA in feline peripheral blood and IFN-ω on antiviral immune response, which may provide strong data support for the development of novel antiviral nanomedicine and the research of the antiviral effects of IFN-ω.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"44 3","pages":"124-134"},"PeriodicalIF":1.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emmanuel Kontomanolis, Christina Tsigalou, Achilleas Mitrakas, Anastasia G Gkegka, Eleni Efraimidou, Dimitrios Karamanidis, Konstantinos Nikoletos, Tsikouras Panagiotis, Nikolaos Nikoletos, Alexandra Giatromanolaki, Michael I Koukourakis
{"title":"Cytokine Plasma Levels in Breast Cancer Patients, Before and After Surgery.","authors":"Emmanuel Kontomanolis, Christina Tsigalou, Achilleas Mitrakas, Anastasia G Gkegka, Eleni Efraimidou, Dimitrios Karamanidis, Konstantinos Nikoletos, Tsikouras Panagiotis, Nikolaos Nikoletos, Alexandra Giatromanolaki, Michael I Koukourakis","doi":"10.1089/jir.2023.0157","DOIUrl":"10.1089/jir.2023.0157","url":null,"abstract":"<p><p>Studying the levels of cytokines in the plasma of patients could be valuable in guiding immunotherapy policies. We assessed the plasma levels of 4 major cytokines [interferon (IFN)-β, interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β)] collected from 19 patients with ductal breast cancer (BCa), before surgery (BS) and 5 days after surgery (AS). The ratio AS/BS was also calculated and correlated with histopathological variables and tumor-infiltrating lymphocyte (TIL) density. The IFN-β and TNF-α levels were significantly higher in BCa patients, BS and AS, than healthy controls (<i>P</i> < 0.02). High IL-2 levels BS were linked with node involvement (<i>P</i> = 0.02), and marginally with HER2 expression (<i>P</i> = 0.08), while high TNF-α levels were linked with high PgR expression (<i>P</i> = 0.02). Increasing IFN-β, IL-2, and TNF-α levels were noted AS, which was more evident in patients with larger tumors. The TGF-β levels were significantly lower in BCa patients (<i>P</i> < 0.007). Linear regression analysis showed a direct association of IFN-β levels AS (<i>P</i> = 0.02, <i>r</i> = 0.52) and of TNF-α AS/BS-ratio (<i>P</i> = 0.001, <i>r</i> = 0.72) with TIL-density. It is suggested that although effector immune response is evident in the majority of early stage BCa patients, removal of the primary tumor further unblocks such responses.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"135-142"},"PeriodicalIF":1.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reham Mohammed Dawood, Ghada Maher Salum, Mai Abd El-Meguid, Basma El-Sayed Fotouh
{"title":"Molecular Insights of Nonalcoholic Fatty Liver Disease Pathogenesis.","authors":"Reham Mohammed Dawood, Ghada Maher Salum, Mai Abd El-Meguid, Basma El-Sayed Fotouh","doi":"10.1089/jir.2023.0162","DOIUrl":"10.1089/jir.2023.0162","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent chronic liver disease. Many hepatic abnormalities are associated with NAFLD such as nonalcoholic steatohepatitis, progressive fibrosis, cirrhosis, and liver failure. Moreover, the pathogenesis of NAFLD has numerous etiologies and can be explained due to the existence of several of stimulus that act simultaneously on genetically susceptible patients. These stimuli include obesity, diabetes, and insulin resistance. In addition, identifying the role of gut microbiota on NAFLD progression has been illustrated. In this review, we clarified the several factors that lead to the development of NAFLD and identify those who are most at risk of developing liver end-stage disease. Highlighting the noninvasive diagnostic NAFLD markers could be helpful in the disease prevention and treatment approaches.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"111-123"},"PeriodicalIF":1.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Richard Salama-Frisbie, Cinthia A Molina-Flores, Arguiñe I Urraza-Robledo, María E Gutiérrez-Pérez, Alberto A Miranda-Pérez, Alhi A Gutiérrez-Salas, Jorge Haro-Santa Cruz, Francisco C López-Márquez
{"title":"Association of Polymorphisms of the <i>IL-17A</i> and <i>IL-17F</i> Genes with Increased Risk of Hypertension and Obesity in Mexican Patients with COVID-19.","authors":"Richard Salama-Frisbie, Cinthia A Molina-Flores, Arguiñe I Urraza-Robledo, María E Gutiérrez-Pérez, Alberto A Miranda-Pérez, Alhi A Gutiérrez-Salas, Jorge Haro-Santa Cruz, Francisco C López-Márquez","doi":"10.1089/jir.2023.0101","DOIUrl":"10.1089/jir.2023.0101","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2). COVID-19 can cause a cytokine release syndrome in which cytokines, including interleukin 17 (IL-17), are massively secreted in response to a specific stimulus. This can contribute to mortality and severe forms of COVID-19. The study aimed to determine the association of SARS-CoV2 infection with the <i>IL-17A</i> rs2275913 and <i>IL-17F</i> rs763780 variants, as well as with the associated comorbidities in COVID-19-positive Mexican patients. The study included 178 patients positive to COVID-19 and 177 COVID-19 negative subjects. For genotyping, the samples were amplified with a TaqMan<sup>®</sup> probe. There was no association between the AA genotype and A allele of IL-17A variant or the <i>IL-17F</i> C allele with the presence of COVID-19. In regard to comorbidities, a statistically significant association was found between <i>IL-17A</i> rs2275913 AA genotype and hypertension, as well as with the presence of obesity (<i>P</i> = 0.003, OR 23, 95% CI: 2.97-178.092 and <i>P</i> = 0.025, OR 28, 95% CI: 1.52-178.029, respectively) in patients with COVID-19. In conclusion, rs2275913 <i>IL-17A</i> polymorphism in COVID-19 patients seems to confer a higher susceptibility to the presence of hypertension and obesity, increasing the risk of premature cardiovascular disease in this population. However, more studies should be conducted for a better understanding of their relation.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"60-67"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cytokines 2023: 11th Annual Meeting of the International Cytokine and Interferon Society.","authors":"Mary McCabe","doi":"10.1089/jir.2023.0207","DOIUrl":"10.1089/jir.2023.0207","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"94-98"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}