Statins and nitric oxide reduce C-reactive protein production while inflammatory conditions persist.
C-reactive protein (CRP) is made in liver and its serum concentration increases in inflammation. Measurement of serum CRP is recommended for use as an indicator of inflammation and predictor of atherosclerosis. Cholesterol-lowering drugs statins also lower CRP. To evaluate statin-mediated CRP reduction and to reassess clinical usefulness of CRP, we investigated regulation of CRP gene expression. Here, we show that pravastatin and simvastatin prevent the induction of CRP expression in human hepatoma Hep3B cells exposed to proinflammatory cytokines IL-6 and IL-1beta The nitric oxide (NO) donor, sodium nitroprusside, also prevented the induction of CRP expression while the CRP inducers IL-6 and IL-1beta were present with the cells. The effect of NO on CRP expression was at the level of transcription. These findings suggest that the decrease in CRP level in vivo after statin-treatment does not necessarily reflect absence of inflammation, and that NO-releasing drugs have the potential to reduce serum CRP levels. Thus, the measurement of serum CRP levels alone in individuals on statin/NO-therapy is not as useful as was imagined.
Voleti
Bhavya
B
Department of Pharmacology, Quillen College of Medicine, P.O. Box 70577, East Tennessee State University, Johnson City, TN 37614, USA.
Agrawal
Alok
A
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D017035:Pravastatin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D009569:Nitric Oxide; D002097:C-Reactive Protein; D019821:Simvastatin; D017035:Pravastatin