Journal of Interferon and Cytokine Research最新文献

Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been found to promote the progression of acute pancreatitis (AP). However, its underlying molecular mechanisms in AP need to be further revealed. Caerulein-induced AR42J cells were used to construct AP cell models. Cell viability and apoptosis were measured by Cell Counting Kit 8 assay and flow cytometry. Levels of inflammatory factors and oxidative stress-related markers were assessed. The medium of AR42J cells was collected for coculturing RAW264.7 cells. Macrophage marker CD86⁺ cell rates were checked with flow cytometry. The levels of TRAF6, embryonic lethal abnormal visual-like protein 1 (ELAVL1), and inducible nitric oxide synthase (iNOS) were examined by Western blot or quantitative real-time polymerase chain reaction. RNA immunoprecipitation assay was performed to evaluate the interaction between ELAVL1 and TRAF6. TRAF6 mRNA stability was tested using actinomycin D treatment. Caerulein treatment suppressed viability, induced AR42J cell apoptosis, inflammation, oxidative stress, and accelerated macrophage M1 polarization. TRAF6 downregulation could alleviate caerulein-induced AR42J cell injury and macrophage M1 polarization. ELAVL1 interacted with TRAF6 to stabilize its expression. Meanwhile, ELAVL1 knockdown relieved caerulein-induced AR42J cell injury and macrophage M1 polarization, while these effects were abolished by TRAF6 overexpression. TRAF6, stabilized by ELAVL1, promoted caerulein-induced AR42J cell injury and macrophage M1 polarization, suggesting that it might accelerate AP9 progression.

Breast cancer (BC) remains one of the most prevalent and deadly malignancies among women globally. A deeper understanding of the molecular mechanisms driving BC progression and metastasis is essential for the development of effective therapeutic strategies. While traditional chemokine receptors are well known for their roles in immune cell migration and positioning, atypical chemokine receptors (ACKRs) have recently gained attention as key modulators in cancer-related processes. Unlike conventional receptors, ACKRs-comprising ACKR1, ACKR2, ACKR3, and ACKR4-primarily function by scavenging chemokines, regulating their availability, and modulating receptor signaling in a ligand-independent manner. This review aims to elucidate the roles of ACKRs in BC, focusing on their influence on the tumor microenvironment (TME), cancer cell proliferation, survival, metastasis, and angiogenesis. Additionally, we will explore the potential of ACKRs as diagnostic and prognostic markers and assess their viability as therapeutic targets. By synthesizing recent research findings and highlighting future research directions, this review seeks to provide a comprehensive understanding of the significance of ACKRs in BC and underscore the need for continued investigation into their therapeutic potential.

Pancreatic cancer (PC) is a cancer with a poor prognosis, and nerve growth factor (NGF) is involved in the pathogenesis of PC within the unknown exact role. Herein, SW1990 cells and PC12 cells were co-cultured using transwell co-culture system and subsequently revealed that NGF was overexpressed in SW1990 cells and promoted PC12 cell proliferation. Knockdown of NGF expression in SW1990 cells using lentiviral shRNA effectively inhibited NGF expression in SW1990 cells and reduced its stimulatory effect on PC12 cell proliferation. Additionally, NGF in SW1990 cells increased the expression of IL-6, dopamine, and c-FOS, as well as decreased the level of lactate dehydrogenase, in PC12 cells, whereas the inhibition of NGF expression significantly reduced the levels of IL-6, dopamine and c-FOS, indicating the critical role of IL-6/STAT3 signaling in PC progression. Finally, cell proliferation, migration, and invasion were assessed using cell counting kit-8, scratch, and Transwell assays, which showed that activated neurons promoted the proliferation, migration, invasion, and NGF secretion of SW1990 cells through the IL-6/STAT3 pathway. The results revealed that NGF secreted by PC cells played a pivotal role in PC progression via regulating activated neural cells-secreted IL-6, providing new theoretical insights for the treatment of PC.

Interleukin-4 (IL-4) controls cell growth and immune system regulation in tumorigenesis and can inhibit the growth of colon cancer cell lines, but the possible mechanism is unclear. In this study, we investigated the possible mechanism of IL-4 in colorectal cancer (CRC) through in vitro experiments. CRC cells received treatment with IL-4 (50 ng/mL), investigating the suppressor of cytokine signaling 1 (SOCS1)-related mechanism underlying the role of IL-4 in the progression and immunosuppression of CRC. The malignant processes of CRC cells and CD8⁺T cell-mediated immune response in CRC cells were determined by CCK-8, Transwell, wound healing, and flow cytometry assays. Programmed death ligand 1 (PD-L1), SOCS1 expressions, and c-Jun N-terminal kinase (JNK) activation in CRC cells were analyzed by quantitative reverse transcription polymerase chain reaction and/or Western blot. IL-4 repressed the malignant processes, yet promoted the apoptosis of CRC cells. Besides, IL-4 downregulated PD-L1 level, upregulated SOCS1 level, and restrained JNK activation in CRC cells, while enhancing CRC cell-killing effect of CD8⁺T cells. IL-4-induced effects on the aforementioned malignant processes of CRC cells and the killing effect of CD8⁺T cells toward CRC cells were all reversed when SOCS1 was knocked down in the CRC cells. IL-4 downregulates PD-L1 level via SOCS1 upregulation-induced JNK deactivation to enhance antitumor immunity in in vitro CRC. The study provides a theoretical basis for the clinical application of IL-4 in antitumor immunity in CRC.

Kidney damage is a serious prevalent complication that occurs after a myocardial infarction (MI) and is associated with worse outcomes. Interleukin-33 (IL-33), a member of the IL-1 superfamily, functions as an alarmin that is released upon necrosis or tissue damage to alert immune cells expressing the ST2L receptor. IL-33 is increased in kidney disease, and recent studies have shown that the IL-33/ST2 axis is instrumental in both disease progression and repair. In this study, we investigated the effect of IL-33 administration on kidneys in C57BL6/J male mice 4 and 7 days after the induction of MI. The mice received either IL-33 or vehicle (PBS) treatment. Cardiac systolic function and systemic inflammation were assessed, and kidneys were subjected to histological and molecular analysis. The administration of IL-33 for 4 days post-MI improved renal structure consistent with reduced expression of profibrotic markers, reduced apoptosis, and increased expression of the anti-inflammatory cytokine IL-4. In addition, IL-33 administration enhanced the levels of Sirtuin3, nicotinamide phosphoribosyltransferase, and the renal nicotinamide adenine dinucleotide pool which are critical for mitochondrial function and energy production, indicating metabolic benefits. However, this protection seems to be lost with the continued administration of IL-33 for 7 days post-MI coinciding with aggravated cardiac dysfunction and increased systemic inflammation. These findings demonstrate that while IL-33 treatment can help improve kidney damage post-MI in the short term, extended treatment may not be beneficial. This may be due to the direct effects of IL-33 on the kidneys or indirectly mediated by adverse cardiac remodeling influencing the cardiorenal crosstalk.

Cytokines are known to be a group of growing small proteins that are majorly responsible for the transmission of signals and communication between hematopoietic cells, the cells of the human immune system, and other types of cells. Cytokines play a dominant role in different types of disorders and in perpetuating the inflammation-related disorders. The production of cytokines is a natural process inside the body of a human being against any foreign invasion or due to some pathogenic state to maintain the homeostasis. Cytokines respond in two ways; in some cases, the production and development of cytokines as a therapeutic discovery or intervention will enhance the treatment process and support the reaction given by the body against any pathogenic activity, and in some cases, overproduction of these cytokines responds in the opposite way and behaves as antagonists toward a typical therapeutic drug and its treatment. Overall, 41 articles were reviewed, and it was found that cytokines have proved to be a therapeutic approach among various diseases and can be utilized as a good candidate or a better choice for cancer therapeutics in future development.

Inefficient control of elevated inflammatory mediators in coronavirus disease 2019 (COVID-19) has led to health complications, prompting the exploration of efficient biomarkers for monitoring this condition. We herein sought to investigate the implications of plasmacytoma variant translocation 1 (PVT-1), microRNA-200c (miR-200c), signal transducer and activator of transcription 4 (STAT-4), and interleukin-6 (IL-6), as well as how they correlated with creatinine, C-reactive protein (CRP), and lactate dehydrogenase (LDH) activity to identify biomarkers able to the early prognosis and diagnosis of COVID-19. Our study included a total of 105 infected COVID-19 patients and 35 healthy subjects as controls. Individuals with COVID-19 showed a significant increase in CRP, creatinine, and LDH activity. In addition, COVID-19 patients exhibited significantly higher levels of IL-6. These patients also demonstrated notably elevated expressions of miR-200c and PVT-1. The expression level of STAT4 decreased in the COVID-19 patients, and this decrease was negatively correlated with creatinine and LDH activity. The levels of miR-200c and PVT-1 expressions, and their connections with IL-6 and STAT4 levels, increased significantly with the severity of COVID-19 cases. In addition, receiver operating characteristic analysis showed that PVT-1 and miR-200c could be reliable biomarkers for determining the severity of COVID-19.

This comprehensive study delved into the pivotal function of chemokine-like receptor 1 (CMKLR1) in lipopolysaccharide (LPS)-triggered epididymo-orchitis in mice. Upon LPS exposure, wild-type (WT) mice exhibited marked elevations in serum pro-inflammatory markers, including G-CSF, IL-6, and RANTES, along with heightened levels of TNF-α and IL-6 in testicular and epididymal tissues, which accompanied by pronounced structural damage within the testicular tissue and a concurrent decline in serum testosterone, estradiol (E2) levels, and testicular steroid synthetase expression. Remarkably, Cmklr1 gene ablation intensified the pro-inflammatory response in the serum (especially IFN-γ), testes, and epididymis of epididymo-orchitis models. Furthermore, Cmklr1 deficiency uniquely induced structural alterations within the epididymis, which is absent in the WT model. This genetic manipulation also exacerbated the decline in serum testosterone and E2 levels and testicular steroid synthase activity. While chemerin levels were significantly diminished in WT epididymo-orchitis models, Cmklr1 knockout had no discernible effect on chemerin expression in the model. In addition, a noteworthy observation was the elevation of the serum low density lipoprotein/high density lipoprotein (LDL/HDL) ratio in Cmklr1-deficient mice. Collectively, these findings underscore that the lack of chemerin/CMKLR1 signaling axis could potentially worsen the symptoms during LPS-induced epididymo-orchitis, highlighting its potential as a therapeutic target in related pathologies.

Membranous nephropathy (MN) is an autoimmune disease that is caused by the production of autoantibody against glomerular podocyte antigens by immune cells due to the lack of self-tolerance mechanisms. Similar to many autoimmune diseases, the pathogenesis of MN is still vague and many experiments are being conducted to detect the antigens and genetic reasons for MN illness. Recently, new antigens, such as exotosin 1/exotosin 2, neural EGF-like-1, semaphorin 3B, and protocadherin 7 have been identified in MN patients who did not have presence of antiphospholipase A2 receptor antigen. What is more, cytokines, which are molecules that regulate immune responses, have been found to have harmful effects in various autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and MN. The role of cytokines and treatment strategies in MN patients is discussed in this article. As the understanding of the disease improves, targeted therapies that focus on specific antigens or cytokines may be developed to effectively manage MN.