Journal of Interferon and Cytokine Research最新文献

Interleukin-17A is a pro-inflammatory cytokine that plays a key role in the immune response to many pathogens and implicated in autoimmune diseases. This molecule is also involved in providing protection to many bacterial and fungal infections of gastro-intestinal tract and respiratory mucosa. Although molecular aspect of IL-17A has been studied in few species, no data are available for buffalo, which is one of the major sources of milk production in India. Therefore, in the present study, IL-17A gene of Indian Murrah Buffalo origin was cloned, expressed, and analyzed using bioinformatic tools. The coding sequence of buffalo IL-17A gene was cloned in prokaryotic expression vector (pET-28a) followed by its expression, purification, and characterization. A computational analysis was performed to understand the sequence, structure, and evolutionary relationship of buIL-17A. It revealed that the length of buIL-17A sequence without signal peptide is 132 amino acids as in cattle. However, sequence identity is found to be 99% due to one amino substitution difference between buffalo and cattle. After analysis, it can be concluded that buIL-17A recombinant protein can be used as a potential immunobiological reagent for diagnostic and therapeutic purpose.

Breast cancer (BC) is a highly prevalent malignancy that poses a significant threat to women's well-being. Novel biomarker identification helps to improve clinical outcomes and provide tailored treatments. Our research aims to explore the diagnostic potential of miR-200a/lncRNA H-19 and interleukin-6 (IL-6)/SIRT-1 axis crosstalk and evaluate the impact of metastasis on gene expression, which provides valuable insights into the diagnosis and treatment of BC. In this case-control study, we collected blood samples from 54 nonmetastatic breast cancer (NMBC) patients, 46 metastatic breast cancer (MBC) patients, and 50 healthy individuals. We used real time-polymerase chain reaction to measure the expression levels of lncRNA H-19 and miR-200a, whereas enzyme linked immunosorbent assay was used to determine the IL-6 levels. In addition, we evaluated SIRT-1 expression level using a Western blot assay. The levels of lncRNA H-19, miR-200a, and IL-6 were higher in BC patients, whereas SIRT-1 levels were lower. Patients with MBC had higher levels of lncRNA H-19, miR-200a, and IL-6 than those with NMBC. In addition, the expression of lncRNA H-19 and miR-200a showed a negative correlation with SIRT-1 expression, whereas the levels of lncRNA H-19 and miR-200a showed a positive correlation with IL-6 expression level. The diagnostic potential of lncRNA H-19 and miR-200a in BC is undeniable. Moreover, the robust association of IL-6/SIRT-1 with lncRNA H-19/miR-200a expression presents a promising opportunity for clinical outcomes and tailored treatments.

Intestinal damage and secondary bacterial translocation are caused by the inflammatory response induced by sepsis. Tongfu Lifei (TLF) decoction has a protective effect on sepsis-related gastrointestinal function injury. However, the relation between gut microbiota, immune barrier, and sepsis under the treatment of TLF have not been well clarified yet. Here, rats were subjected to cecal ligation and puncture (CLP) to create a sepsis model. Subsequently, the TLF decoction was given to CLP rats by gavage, fecal microbiota transplantation (FMT), and antibiotic were used as positive control. TLF suppressed the inflammatory response and improved the pathological changes in the intestines of CLP rats. Besides, TLF promoted the balance of the percentage of the Th17 and Treg cells. Intestinal barrier function was also improved by TLF through enhancing ZO-1, and Occludin and Claudin 1 expression, preventing the secondary translocation of other gut microbiota. TLF dramatically boosted the gut microbiota's alpha- and beta-diversity in CLP rats. Moreover, it increased the relative abundance of anti-inflammatory gut microbiota and changed the progress of the glucose metabolism. In short, TLF regulated the gut microbiota to balance the ratio of Th17/Treg cells, reducing the inflammation in serum and intestinal mucosal injury in rats.

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.

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, in vitro. The results showed that expression of interleukin (IL) 1B, IL9, and IL12A-B was increased by 2-fold, while IL18 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 IL 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, IL1A-B and IL6 or cytokine genes associated with supporting tumor progression, leukemia stem cell growth or poor survival, such as IL3, IL8, IL9, IL10, IL12, or IL15. 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 IL2, IL6, IL15, IFNG, 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.

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.

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.

The goal of the current study was to assess levels of salivary interleukin (IL)-38, IL-1β, and IL-10 in various periodontal clinical conditions. In total, 60 (20 healthy, 20 gingivitis, and 20 stage II-III, grade A-B periodontitis) subjects were included in the study. Demographic and clinical periodontal parameters were recorded. Samples were examined for IL-38, IL-1β, and IL-10 levels by means of enzyme-linked immunosorbent assay. Results demonstrated that the periodontitis group had significantly lower salivary IL-38 levels (P < 0.05) than the healthy group. Salivary IL-10 levels did not differ significantly between the groups (P > 0.05). The salivary IL-1β levels of gingivitis (P < 0.001) and periodontitis groups (P < 0.01) were significantly higher than those of the healthy group. The present study indicated that IL-38 level is decreased in periodontal disease. The results suggested a possible role of IL-38 in the periodontal inflammation process. Clarifying the mechanisms of IL-38 in the inflammatory process may contribute to the development of novel treatment strategies in periodontal diseases.

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.