Journal of Interferon and Cytokine Research最新文献

Sepsis is a clinically life-threatening syndrome, and acute lung injury is the earliest and most serious complication. We aimed to assess the role of kruppel-like factor 13 (KLF13) in lipopolysaccharide (LPS)-induced human alveolar type II epithelial cell damage and to reveal the possible mechanism related to peroxisome proliferator-activated receptor-γ co-activator 1-α (PGC-1α). In LPS-treated A549 cells with or without KLF13 overexpression or PGC-1α knockdown, cell viability was measured by a cell counting kit-8 assay. Enzyme-linked immunosorbent assay kits detected the levels of inflammatory factors, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining measured cell apoptosis. Besides, mitochondrial reactive oxygen species (MitoSOX) and mitochondrial membrane potential were detected using MitoSOX red- and JC-1 staining. Expression of proteins related to mitochondrial quality control (MQC) was evaluated by western blot. Co-immunoprecipitation (Co-IP) assay was used to analyze the interaction between KLF13 and PGC-1α. Results indicated that KLF13 was highly expressed in LPS-treated A549 cells. KLF13 upregulation elevated the viability and reduced the levels of inflammatory factors in A549 cells exposed to LPS. Moreover, KLF13 gain-of-function inhibited LPS-induced apoptosis of A549 cells, accompanied by upregulated BCL2 expression and downregulated Bax and cleaved caspase3 expression. Furthermore, MQC was improved by KLF13 overexpression, as evidenced by decreased MitoSOX, JC-1 monomers and increased JC-1 aggregates, coupled with the changes of proteins related to MQC. In addition, Co-IP assay confirmed the interaction between KLF13 and PGC-1α. PGC-1α deficiency restored the impacts of KLF13 upregulation on the inflammation, apoptosis, and MQC in LPS-treated A549 cells. In conclusion, KLF13 attenuated LPS-induced alveolar epithelial cell inflammation and apoptosis by regulating MQC via binding PGC-1α.

Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by epidermal thickening and inflammatory cell infiltration. Excessive proliferation of keratinocytes and resistance to apoptosis lead to thickening of the epidermis. Plasmacytoid dendritic cells are involved in the occurrence of psoriasis mainly by secreting interferon-alpha (IFN-α). IFN-α is a glycoprotein with antiviral, antitumor, and immunomodulatory effects, but its role in psoriasis remains unclear. In this investigation, a mild psoriatic phenotype was observed in mice upon topical application of IFN-α cream, and the inflammation was exacerbated when combined with imiquimod (IMQ). Immunohistochemical analyses demonstrated that IFN-α induces psoriatic inflammation in mice by stimulating phosphorylation of forkhead box O3, consistent with the involvement of this protein in cell proliferation, apoptosis, and inflammation. Our results suggested that topical IFN-α caused psoriatic inflammation and that the psoriatic inflammation was exacerbated by the combination of IFN-α and IMQ, possibly due to the dysfunction of forkhead box O3.

Cell-mediated immune response is critical for Mycobacterium tuberculosis (M.tb) control. Understanding of pathophysiology and role played by different cell mediators is essential for vaccine development and better management of patients with M.tb. A complex array of cytokines and chemokines are involved in the immune response against M.tb; however, their relative contribution in protection remains to be further explored. The purpose of this review is to summarize the current understanding regarding the cytokine and chemokine profiles in M.tb infection in order to assist research in the field to pursue new direction in prevention and control. We have also summarized recent findings on vaccine trials that have been developed and or are under trials that are targeting these molecules.

The recombinant human interferon alpha-2b (IFN-α2b) nasal drop formulation (Nasalferon) was studied as prophylaxis for SARS-CoV-2. Healthy volunteers between 19 and 80 years of age received 0.5 million international units of IFN in one drop (0.05 mL ) in each nostril, twice a day, for 10 consecutive days. The nondetection of SARS-CoV-2 by real-time polymerase chain reaction was the primary outcome variable. Several IFN-α biomarkers, including intranasal gene expression and innate immune effector activity, were increased in participants who received intranasal IFN-α2b. The study included 2,930 international travelers and 5,728 persons who were their close contacts. The subjects were treated with Nasalferon in January 2021, and 9,162 untreated travelers were included as controls. COVID-19 rate in treated subjects was significantly lower than in untreated subjects (0.05% vs. 4.84%). The proportion of travelers with COVID-19 decreased from 60.9% to 2.2% between December 2020 and February 2021. Furthermore, 1,719 tourism workers also received Nasalferon, and no cases of SARS-CoV-2 infection were detected, whereas 39 COVID-19 cases (10.6%) were reported in 367 untreated subjects. The main adverse events associated with the use of intranasal IFN-α2b were nasal congestion, headache, and rhinorrhea. Our prophylactic health interventions study demonstrates that the daily administration of Nasalferon for 10 days decreases the risk of developing COVID-19 in healthy volunteers. [Figure: see text].

Chronic low-grade inflammation (CLI) is implicated in the development of multiple metabolic diseases. The gut microbiota (GM) activates different signaling pathways and induces phenotypic changes, offering an exciting opportunity to treat CLI. We evaluated the mediation of waist circumference on the association of GM with serum cytokines. In this cross-sectional study of 331 children, we measured 5 gut bacterial species, namely, Lactobacillus (L.) casei, L. paracasei, L. reuteri, Staphylococcus (S.) aureus, and Akkermansia (A.) muciniphila, as well as anthropometry, serum cytokines, and other covariates. We evaluated adjusted regression models, path analysis, and structural equation modeling to obtain path coefficients (PCs) for direct, indirect (waist circumference-mediated), and total effects. We found that L. paracasei was directly associated with lower interleukin-10 (IL-10) levels (PC = -173.5 pg/mL). We also observed indirect associations between S. aureus with lower adiponectin levels (PC = -0.1 µg/mL and -0.09 µg/mL). Finally, A. muciniphila was indirectly associated with higher adiponectin levels (PC = 0.1 µg/mL). Our findings suggest the importance of considering the GM composition and waist circumference when evaluating inflammatory-related factors, providing a basis for future research to identify potential strategies to intervene in inflammatory processes and prevent metabolic diseases in childhood. [Figure: see text].

Hepatitis C virus (HCV) infection is a global health concern affecting millions worldwide. Chronic HCV infection often leads to liver inflammation and can progress to cirrhosis and hepatocellular carcinoma. Inflammatory cytokines are crucial in modulating the immune response during HCV infection. This review aims to investigate the impact of different inflammatory cytokines on HCV infection and associated immune responses. This review was conducted to identify relevant studies on the interplay between inflammatory cytokines and HCV infection. The analysis focused on the effects of key inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 (IL-1), and interferon-gamma (IFN-γ), on HCV replication, immune cell activation, and liver inflammation. The findings reveal that these inflammatory cytokines can significantly influence HCV infection and the subsequent immune response. TNF-α, IL-6, and IL-1 have been shown to enhance HCV replication, while IFN-γ exerts antiviral effects by inhibiting viral replication and promoting immune cell-mediated clearance of infected hepatocytes. Moreover, these cytokines contribute to the recruitment and activation of immune cells, such as natural killer cells, T cells, and macrophages, which play critical roles in controlling HCV infection. Understanding the precise mechanisms by which inflammatory cytokines impact HCV infection is crucial for developing more targeted therapeutic strategies. Modulating the levels or activity of specific cytokines may provide opportunities to attenuate HCV replication, reduce liver inflammation, and improve treatment outcomes. In conclusion, this review highlights the significance of inflammatory cytokines in influencing HCV infection and associated immune responses.

Melanoma, an infrequent yet significant variant of skin cancer, emerges as a primary cause of brain metastasis among various malignancies. Despite recognizing the involvement of inflammatory molecules, particularly chemokines, in shaping the metastatic microenvironment, the intricate cellular signaling mechanisms underlying cerebral metastasis remain elusive. In our pursuit to unravel the role of cytokines in melanoma metastasis, we devised a protocol utilizing mixed cerebral cortical cells and SK-MEL-28 melanoma cell lines. Contrary to expectations, we observed no discernible morphological change in melanoma cells exposed to a cerebral conditioned medium (CM). However, a substantial increase in both migration and proliferation was quantitatively noted. Profiling the chemokine secretion by melanoma in response to the cerebral CM unveiled the pivotal role of interferon gamma-induced protein 10 (CXCL10), inhibiting the secretion of interleukin 8 (CXCL8). Furthermore, through a transwell assay, we demonstrated that knockdown CXCL10 led to a significant decrease in the migration of the SK-MEL-28 cell line. In conclusion, our findings suggest that a cerebral CM induces melanoma cell migration, while modulating the secretion of CXCL10 and CXCL8 in the context of brain metastases. These insights advance our understanding of the underlying mechanisms in melanoma cerebral metastasis, paving the way for further exploration and targeted therapeutic interventions.

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.