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Protein kinase A suppresses anti-proliferative effect of interferon-α in hepatocellular carcinoma by activation of protein tyrosine phosphatase SHP2.
J Biol Chem
January 2025
Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China. Electronic address:
Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) plays a dual role in cancer initiation and progression. Identifying signals that modulate the function of SHP2 can improve current therapeutic approaches for IFN-α/β in HCC. We showed that cAMP-dependent protein kinase A (PKA) suppresses IFN-α/β-induced JAK/STAT signaling by increasing the phosphatase activity of SHP2, promoting the dissociation of SHP2 from the receptor for activated C-kinase 1 (RACK1) and binding to STAT1.
View Article and Find Full Text PDFBovine Lactoferrin Enhances Toll-like Receptor 7 Response in Plasmacytoid Dendritic Cells and Modulates Cellular Immunity.
Int J Mol Sci
December 2024
Department of Molecular Pathophysiology, Wakayama Medical University, Wakayama 641-8509, Japan.
Plasmacytoid dendritic cells (pDCs) express Toll-like receptor 7 (TLR7) in the endosomes, recognize viral single-stranded RNA (ssRNA), and produce significant amounts of interferon (IFN)-α. Bovine lactoferrin (LF) enhances the response of IFN regulatory factors followed by the activation of IFN-sensitive response elements located in the promoter regions of the gene and IFN-stimulated genes in the TLR7 reporter THP-1 cells in the presence of R-848, a TLR7 agonist. In ex vivo experiments using human peripheral blood mononuclear cells, LF enhances IFN-α levels in the supernatant in the presence of R-848.
View Article and Find Full Text PDFIFN alpha signaling drives hematopoietic stem cells malfunction under acute inflammation.
Int Immunopharmacol
February 2025
Department of Hematology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. Electronic address:
Article Synopsis
- Inflammation triggers the activation of hematopoietic stem cells (HSCs) via direct sensing of lipopolysaccharide (LPS) through toll-like receptor 4 (TLR4) and cytokine release.
- The study found that LPS stimulation leads to the activation of the interferon alpha (IFNα) signaling pathway, resulting in both the activation and eventual exhaustion of HSCs.
- Creatine, an inhibitor of IFNα, can prevent HSC activation and exhaustion caused by LPS, while a deficiency in the IFNα receptor (IFNAR) offers protection to HSCs during inflammation, indicating that LPS injuries HSCs through both direct and indirect pathways.
Self-assembled eumelanin nanoparticles enhance IFN-I activation and cilia-driven intercellular communication to defend against Tulane virus, a human norovirus surrogate.
Biomater Sci
January 2025
Department of Food Science & Technology, Faculty of Science, National University of Singapore, 117546, Singapore.
Norovirus (NoV) infection is a leading cause of gastroenteritis and poses global health threats, with increasing incidence reported in immunocompromised individuals, which is further exacerbated by the globalization of the food industry. Eumelanin has demonstrated its potential in antiviral treatments, but its role in preventing viral infections remains underexplored. Therefore, in this study, we investigated the antiviral properties and potential mechanisms of self-assembled eumelanin nanoparticles (EmNPs) against Tulane virus (TuV), a surrogate with a similar infection mechanism to NoVs.
View Article and Find Full Text PDFInterferon-Dependent Expression of the Human STAT1 Gene Requires a Distal Regulatory Region Located Approximately 6 kb Upstream for Its Autoregulatory System.
Genes Cells
January 2025
Department of Anatomy and Cell Biology, Research Institute of Pharmaceutical Science, Faculty of Pharmacy, Musashino University, Tokyo, Japan.
We previously suggested that the signal transducer and activator of transcription 1 (STAT1) gene is autoregulated in an interferon (IFN)-dependent manner via a distal regulatory region approximately 5.5-6.2 kb upstream of the murine and human STAT1 promoters (designated 5.
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