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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Aorta, C-Reactive Protein, Carcinoma, Hepatocellular, Cell Line, Cell Line, Tumor, Endothelial Cells, Endothelium, Vascular, Enzyme Activation, Gene Expression Regulation, Hepatocytes, Humans, Interleukin-1, Interleukin-6, Interleukin-8, Liver Neoplasms, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Phorbol 12,13-Dibutyrate, Promoter Regions, Genetic, Protein Kinase C, Protein Kinase C beta, Transcription, Genetic, Umbilical Veins.
user
Is protein kinase C pathway involved in transcriptional regulation of C-reactive protein synthesis in human hepatocytes? Context: C-reactive protein (CRP) is the prototype acute phase protein and a cardiovascular risk factor. Interleukin-1beta (IL-1beta) and IL-6 stimulate CRP synthesis in hepatocytes. We searched for additional pathways regulating CRP expression. Primary human hepatocytes (PHHs) were treated with IL-1beta, IL-6, and protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBu). CRP was analyzed by quantitative RT-PCR and ELISA. PDBu significantly induced CRP transcription by 21.0+/-9.24-fold and protein release by 2.9+/-0.5-fold. Transcriptional regulation was studied in detail in hepatoma G2 (HepG2) cells stably transfected with the 1-kb CRP promoter (HepG2-ABEK14 cells). In these cells, PDBu significantly induced CRP transcription by 5.39+/-0.66-fold. Competitive inhibition with bisindolylmaleimide derivative LY333531 abolished PDBu-mediated promoter activation. Competitive inhibition with IkappaB kinase inhibitor I229 also inhibited PDBu effects. Importantly, IL-8 significantly induced CRP release in PHHs by 58.675+/-19.1-fold, which was blockable by LY333531.
assistant
This study describes a novel PKC-dependent transcriptional regulation of CRP gene expression, which, in analogy to the classical IL-1beta and IL-6 pathways, is operational in hepatocytes only. It also identifies IL-8 as a potential physiological PKC activator. HepG2-ABEK14 cells may be useful for high throughput screening to identify inhibitors of CRP synthesis for the prevention of cardiovascular disease. Final Decision: yes