Involvement of Interferon Regulatory Factor 7 in Nicotine ’s Suppression of Antiviral Immune Responses

AbstractNicotine, the active ingredient in tobacco smoke, suppresses antiviral responses. Interferon regulatory factors (IRFs) regulate transcription of type I interferons (IFNs) and IFN-stimulated genes (ISGs) in this response. IRF7 is a key member of the IRF family. Expression ofIrf7 is elevated in the brains of virus-infected animals, including human immunodeficiency virus-1 transgenic (HIV-1Tg) rats. We hypothesized that IRF7 affects nicotine ’s modulation of antiviral responses. Using CRISPR/Cas9 system,IRF7-mutant cell lines were created from human embryonic kidney 293FT cells in which 16 nicotinic acetylcholine receptors (nAChRs) were detected. Decreased expression of IRF7 was confirmed at both the mRNA and protein levels, as wasIRF7-regulated cell growth in twoIRF7-mutant cell lines, designatedIRF7- Δ7 andIRF7- Δ11. InIRF7- Δ7 cells, expression of two nAChR genes,CHRNA3 andCHRNA9, changed modestly. After stimulation with polyinosinic –polycytidylic acid (poly I:C) (0.25 μg/ml) for 4 h to mimic viral infection, 293FT wild-type (WT) andIRF7- Δ7 cells were treated with 0, 1, or 100 μM nicotine for 24 h, which increased IFN-β expression in both types of cells but elevation was higher in WT cells (p 
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research

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te;lez-Espinosa C Abstract Hypoxia is a condition that together with low pH, high amounts of reactive oxygen species (ROS), and increased adenosine levels characterize tumor microenvironment. Mast cells (MCs) are part of tumor microenvironment, but the effect of hypoxia on the production of MC-derived cytokines has not been fully described. Using the hypoxia marker pimonidazole in vivo, we found that MCs were largely located in the low-oxygen areas within B16-F1 mice melanoma tumors. In vitro, hypoxia promoted ROS production, a ROS-dependent increase of intracellular calcium, and the production of MCP 1 (CCL-2) in...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research
CONCLUSIONS: Tablysin-15 has reliable anti-cancer effects against M21 melanoma cells, suggesting tablysin-15 is a promising anti-tumor drug. PMID: 31893992 [PubMed - as supplied by publisher]
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research
Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein homologous to angiopoietins. Previous studies suggest that tumor cell-derived ANGPTL2 has tumor-promoting function. Here, we conducted mechanistic analysis comparing ANGPTL2 function in cancer progression in a murine syngeneic model of melanoma and a mouse model of translocation renal cell carcinoma (tRCC). ANGPTL2 deficiency in tumor cells slowed tRCC progression, supporting a tumor-promoting role. However, systemic ablation of ANGPTL2 accelerated tRCC progression, supporting a tumor-suppressing role. The syngeneic model also demonstrated a tumor-suppressing...
Source: Genes and Development - Category: Genetics & Stem Cells Authors: Tags: Research Papers Source Type: research
n-Anezin Oncogene-induced STAT3-activation is central to tumor progression by promoting cancer cell expression of pro-angiogenic and immunosuppressive factors. STAT3 is also activated in infiltrating immune cells including tumor-associated macrophages (TAM) amplifying immune suppression. Consequently, STAT3 is considered as a target for cancer therapy. However, its interplay with other STAT-family members or transcription factors such as NF-κB has to be considered in light of their concerted regulation of immune-related genes. Here, we discuss new attempts at re-educating immune suppressive tumor-associated m...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Abstract Earlier studies from our laboratory have demonstrated that Oxyresveratrol (OXY), a hydroxyl-substituted stilbene, exhibits potent inhibition of human melanoma cell proliferation. The present study defines a cytotoxic effect of OXY on the highly chemo-resistant, triple-negative human breast cancer cell line MDA-MB-231. OXY-mediated cell death resulted in accumulation of cells at the sub-G1 phase of the cell cycle, induced chromatin condensation, DNA fragmentation, phosphatidylserine externalization and PARP cleavage, indicative of apoptosis. Interestingly, morphology and cell viability studies with the pan...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
Cancers, Vol. 11, Pages 1806: Complex Formation with Monomeric α-Tubulin and Importin 13 Fosters c-Jun Protein Stability and Is Required for c-Jun’s Nuclear Translocation and Activity Cancers doi: 10.3390/cancers11111806 Authors: Melanie Kappelmann-Fenzl Silke Kuphal Rosemarie Krupar Dirk Schadendorf Viktor Umansky Lily Vardimon Claus Hellerbrand Anja-Katrin Bosserhoff Microtubules are highly dynamic structures, which consist of α- and β-tubulin heterodimers. They are essential for a number of cellular processes, including intracellular trafficking and mitosis. Tubulin-b...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ie Bogaerts Melittin (MEL), a small peptide component of bee venom, has been reported to exhibit anti-cancer effects in vitro and in vivo. However, its clinical applicability is disputed because of its non-specific cytotoxicity and haemolytic activity in high treatment doses. Plasma-treated phosphate buffered saline solution (PT-PBS), a solution rich in reactive oxygen and nitrogen species (RONS) can disrupt the cell membrane integrity and induce cancer cell death through oxidative stress-mediated pathways. Thus, PT-PBS could be used in combination with MEL to facilitate its access into cancer cells and to reduce the r...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Conclusions: In conjunctival melanoma, nuclear localization and activation of β-catenin appear to be limited, suggesting that inhibition of ARF6, responsible for β-catenin activation, in subsets of skin melanoma may not represent a treatment option for this tumor. In vitro, Wnt3a or Wnt5a did not induce nuclear β-catenin localization.Dermatopathology 2019;6:50 –62
Source: Dermatopathology - Category: Pathology Source Type: research
Conclusion: These findings provide a novel insight into the role of the Sox2 gene in tumor cell stemness, tumor dormancy, and apoptosis.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
CONCLUSION: GNP-HER2 can selectively kill G361 melanoma cells without affecting normal cells. The mechanism of G361 cell death upon treatment with GNP-HER2 was apoptosis accompanied by activation of caspases. PMID: 31124333 [PubMed - in process]
Source: Yonsei Medical Journal - Category: Universities & Medical Training Authors: Tags: Yonsei Med J Source Type: research
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