In A-431 cells, platelet-activating factor (PAF) induces the expression of c-fos and TIS-1 genes in both the absence and the presence of cycloheximide in a structurally specific and receptor-coupled manner. We have now investigated the molecular mechanisms of this response, particularly in relation to the role of protein kinases. Pretreatment of cells with genistein or methyl-2,5-dihydroxycinnamate (tyrosine kinase inhibitors) or staurosporine (a protein kinase C inhibitor) for 20 min abolished the c-fos expression induced by PAF. Interestingly, when genistein was added 90 s after addition of PAF, no inhibition was observed. Similarly, staurosporine did not inhibit c-fos expression when added 8 min after PAF addition to the cells. These inhibitions were dose-dependent (IC50 for staurosporine was 180 nM, and for genistein 50 microM). Simultaneous addition of PAF and phorbol 12-myristate 13-acetate (PMA) did not give a synergistic effect on c-fos expression. Pretreatment of cells with PMA had no effect on [3H]PAF binding, but abolished the PAF-induced gene expression. PAF-stimulated gene expression was desensitized if cells were pretreated with PAF. Interestingly, epidermal growth factor was able to stimulate c-fos expression in PAF-desensitized cells, and thus indicated involvement of distinct mechanisms for the two stimuli. Forskolin, an activator of adenylate cyclase, did not induce c-fos expression and had no effect on the PAF response. Exposure of cells to PAF for as little as 1 min, followed by its removal, was sufficient to activate the gene expression and demonstrated the rapidity and the exquisite nature of the signalling involved in this process. It is concluded that activation of PAF receptor (a proposed G-protein-coupled receptor) causes rapid production of signals which induce the expression of c-fos gene and that this is mediated via tyrosine kinase and protein kinase C.
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http://dx.doi.org/10.1042/bj2860527 | DOI Listing |
Cell Mol Gastroenterol Hepatol
January 2025
Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine at University of Pennsylvania. Electronic address:
Background & Aims: Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory disorder characterized by eosinophil-rich mucosal inflammation and tissue remodeling. Prior research has revealed the upregulation of interferon (IFN) response signature genes (ISGs) in biopsy tissue from EoE patients, but the specific cell types that contribute to this IFN response and the effect of interferons on the esophageal epithelium remain incompletely understood. Here, we use scRNA-seq to examine the expression of IFN and ISGs during EoE and explore how IFN-α and IFN-γ treatments affect epithelial function.
View Article and Find Full Text PDFNeurochem Res
January 2025
Department of Orthopaedics, Tianjin Hospital, Tianjin University, Tianjin, China.
Neuropathic pain (NP) imposes a significant burden on individuals, manifesting as nociceptive anaphylaxis, hypersensitivity, and spontaneous pain. Previous studies have shown that traumatic stress in the nervous system can lead to excessive production of hydrogen sulfide (HS) in the gut. As a toxic gas, it can damage the nervous system through the gut-brain axis.
View Article and Find Full Text PDFCell Mol Neurobiol
January 2025
Department of Neurology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
Neuropathic pain, a prevalent complication following spinal cord injury (SCI), severely impairs the life quality of patients. No ideal treatment exists due to incomplete knowledge on underlying neural processes. To explore the SCI-induced effect on nociceptive circuits, the protein expression of c-Fos was analyzed as an indicator of neuronal activation in a rat contusion model exhibiting below-level pain.
View Article and Find Full Text PDFBehav Brain Res
January 2025
Laboratorio de Neurociencias, Facultad de Psicología, Universidad de Colima, Colima, Mexico 28040. Electronic address:
Tactile information from the whiskers (vibrissae) travels through the somatosensory cortex to the entorhinal cortex and the hippocampus, influencing development and psychological well-being. The lack of whiskers affects cognitive functions, spatial memory, neuronal firing, spatial mapping, and neurogenesis in the dorsal hippocampus. Recent studies underline the importance of tactile experiences in emotional health, noting that while tactile stimuli modulate the dorsal hippocampus, the effects of tactile deprivation on anxiety-like behaviors and neural activity in regions like the ventral hippocampus and amygdala are less understood.
View Article and Find Full Text PDFJ Dent Sci
January 2025
Department of Dentistry, Yeungnam University College of Medicine, Daegu, Republic of Korea.
Background/purpose: Membrane-free stem cell components (MFSCCs) have been developed by removing cell membranes with antigens to overcome the limitations associated with cell-based therapies and isolate effective peptides. MFSCCs have been reported to have effects on oral infection sites. Chronic inflammatory diseases cause excessive bone resorption.
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