Journal of Interferon and Cytokine Research最新文献

Interferon-gamma (IFN-γ) is an important cytokine associated with antitumor immunity and has been implicated in the pathogenesis and progression of lung cancer. Nevertheless, no bibliometric analyses have been published in this field to date, and thus we aim to address this gap in knowledge. A search of the Web of Science (WOS) for literature related to the treatment of lung cancer with IFN-γ was conducted from 2002 to 2024. The extracted information from the included articles was subjected to visual analysis, and network diagrams were generated using software such as CiteSpace and VOSviewer. In total, 589 articles related to the treatment of lung cancer with IFN-γ were included in WOS between 2002 and 2024. The number of articles and citation frequency generally showed an increasing trend year by year. The United States and the University of California are the countries and institutions with the largest number of articles. The researcher who made the largest contribution to this field was Xin Cai from China (6). The Journal for ImmunoTherapy of Cancer published the largest number of relevant papers in the field (16 papers, IF = 12.469). The research hotspots in the field of immune escape in recent years have been IFN-γ, mechanism, immune checkpoints, and microtumor inhibitors. The field of IFN-γ treatment of lung cancer is evolving at a rapid pace. The current research focus within this field is on elucidating the mechanism of IFN-γ treatment of lung cancer, investigating the role of immune checkpoint inhibitors, and examining the tumor microenvironment and other pertinent topics.

The suppressors of cytokine signaling (SOCS) genes were first described in a group of articles published in 1997. Since that time, much has been learned about the functional activities mediated by the corresponding proteins encoded by the SOCS genes. The SOCS gene family contains eight members: SOCS1 through SOCS7 and a highly related gene known as CISH (cytokine-inducible SH2-containing protein). Although much is known about the ability of the SOCS proteins to autoregulate responses to individual cytokines, much less is known about the ability of the SOCS proteins to cross-regulate cytokine signaling. The studies described in a new report by Bidgood et al. in this issue of JICR demonstrate that SOCS1 expression induced by one cytokine, interferon (IFN)-γ, can cross-regulate signaling induced by another cytokine, granulocyte macrophage colony-stimulating factor (GM-CSF), in murine bone marrow-derived macrophages. The authors show that the ability of SOCS1 to inhibit cytokine signaling is dose- and time-dependent. SOCS1 must reach a critical threshold level before it can exert a marked inhibitory effect on autocrine signaling through the IFN-γ receptor or paracrine signaling through the GM-CSF receptor.

Recent studies have revealed that formononetin, a naturally occurring isoflavone found in kudzu root and licorice, has the potential to inhibit ferroptosis in intestinal epithelial cells. Inflammatory bowel disease (IBD) often involves oxidative stress-related pathways, making the modulation of ferroptosis a promising therapeutic avenue. We employed a combination of several techniques to explore how formononetin regulates the retinoid X receptor alpha/peroxisome proliferator activated receptor gamma (RXRA/PPARG) pathway to inhibit ferroptosis in Fetal Human Colonic Epithelial Cells (FHC) induced by RSL3. These techniques included propidium iodide staining, the levels of reactive oxygen species (ROS), Fe²⁺, malondialdehyde (MDA), and ferroptosis-inhibitory proteins glutathione peroxidase 4 (GPX4) and FTH analysis, Western blot analysis, and gene silencing. Our results demonstrate that formononetin significantly mitigated RSL3-induced ferroptosis as evidenced by reduced cellular levels of ROS, Fe²⁺, and MDA, alongside an increased expression of GPX4 and FTH. Silencing the RXRA gene reverses the protective effects of formononetin, highlighting that formononetin inhibits ferroptosis in FHC by upregulating the levels of RXRA. These findings provide new molecular targets for potential therapeutic intervention in IBD, suggesting that upregulating RXRA and PPARG expression via formononetin could be a viable strategy to mitigate ferroptosis-associated cellular damage. This could potentially lead to novel treatments for patients suffering from IBD.

Suppressor of cytokine signaling (SOCS) 1 is a key negative regulator of interferon (IFN), interleukin (IL)12, and IL-2 family cytokine signaling through inhibition of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. To investigate the temporal induction of SOCS1 in response to cytokine in live cells and its selective regulation of signaling pathways, we generated a mouse expressing a Halo-tag-SOCS1 fusion protein (Halo-SOCS1) under control of the endogenous Socs1 promoter. Homozygous Halo-SOCS1 mice (Halo-Socs1^KI/KI) were viable with minor T cell abnormalities, most likely due to enhanced Halo-SOCS1 expression in thymocytes compared with the untagged protein. IFNγ and IL-4 induced Halo-SOCS1 expression in macrophages derived from Halo-Socs1^KI/KI mice, and a critical level of SOCS1 expression was required for inhibition of both IFNγ and granulocyte macrophage-colony stimulating factor (GM-CSF)-driven JAK-STAT signaling. In contrast, IFNγ priming to induce SOCS1 did not cross-regulate IL-4 signaling. This study indicates that while SOCS1 expression needs to exceed a critical threshold to inhibit IFNγ signaling, its selective regulation of cytokine signaling results from an as yet undetermined, level of regulatory control.

Background: This study was designed to explore the action mechanism of stimulator of interferon genes (STING) on the differentiation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment of lung cancer. Methods: Bioinformatics analysis yielded a potential pathway for STING to regulate MDSC differentiation, the interferon regulatory factor 3 (IRF3)/NF-κB axis. The transfection efficiency of STING overexpression plasmid and small interfering RNA against IRF3 (siIRF3) was examined by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection, A9 cells were co-cultured with extracted bone marrow cells (BMCs). MDSC differentiation, protein expression of the IRF3/NF-κB pathway, and changes in nuclear translocation of NF-κB were analyzed by flow cytometry, Western blot, and immunofluorescence staining experiments. A transplanted tumor mouse model was used for in vivo experiments. After cyclic diadenyl monophosphate (CDA; STING agonist) treatment, changes in MDSC differentiation and protein expression of the IRF3/NF-κB axis in transplanted tumors were verified by immunohistochemical staining, qRT-PCR, and Western blot. Results: Coculture of A9 cells and BMCs promoted MDSC differentiation, inhibited activation of IRF3/NF-κB signal in A9 cells, and boosted nuclear translocation of NF-κB. However, after the upregulation of STING, IRF3/NF-κB signal was activated, while MDSC differentiation and nuclear translocation of NF-κB were inhibited. SiIRF3 reversed the effects of STING overexpression. In vivo, CDA dampened MDSC differentiation and promoted protein expression of the IRF3/NF-κB axis. Conclusion: STING signal in lung cancer cells inhibits MDSC differentiation through activation of the IRF3/NF-κB pathway.

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.

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.

The causal relationship between inflammatory factors and acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced acute pancreatitis (AAP), and alcohol-induced chronic pancreatitis (ACP) remains unclear. We aimed to examine the casual relationship between inflammatory factors and various forms of pancreatitis, namely, AP, CP, AAP, and ACP. We employed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between 91 inflammatory factors and 41 inflammatory factors with respect to pancreatitis. The primary analysis involved the use of the inverse variance weighting (IVW). MR-Egger intercept test, Cochran's Q test, MR-PRESSO test, and Leave-One-Out analysis were used to assess the robustness of our findings. IVW analysis revealed evidence of association between 24 inflammatory cytokines and pancreatitis. Specifically, six cytokines were associated with AP, eight cytokines were associated with CP, three cytokines were associated with AAP, and seven cytokines were associated with ACP. The most significant associations were observed with β nerve growth factor (odds ratio [95% confidence interval]: 6.05 [1.59, 23.01]) and interleukin-4 [IL-4; 2.56 (0.91, 7.16)] in AAP, as well as interleukin-2 receiver subunit beta and IL-4 in ACP. Our findings suggest that certain inflammatory cytokines may have a significant role in the development of pancreatitis.