Simvastatin acts as an inhibitor of interferon gamma-induced cycloxygenase-2 expression in human THP-1 cells, but not in murine RAW264.7 cells. Biocell : official journal of the Sociedades Latinoamericanas de Microscopía Electronica ... et. al [Biocell] Journal article

Title	Simvastatin acts as an inhibitor of interferon gamma-induced cycloxygenase-2 expression in human THP-1 cells, but not in murine RAW264.7 cells.
Author(s)	Lee CS, Shin YJ, Won C, Lee YS, Park CG, Ye SK, Chung MH
Institution	Department of Pharmacology, Seoul National University, College of Medicine, Seoul 110-799, Korea.
Source	Biocell 2009 Aug; 33(2):107-14.
Abstract	Cyclooxygenase-2 (COX-2) is a key inflammatory response molecule, and associated with many immune functions of monocytes/macrophages. Particularly, interferon gamma (IFNgamma)-induced COX-2 expression appears in inflammatory conditions such as viral infection and autoimmune diseases. Recently, statins have been reported to show variable effects on COX-2 expression, and on their cell and species type dependences. Based on the above description, we compared the effect of simvastatin on IFNgamma-induced COX-2 expression in human monocytes versus murine macrophages. In a result, we found that simvastatin suppresses IFNgamma-induced COX-2 expression in human THP-1 monocytes, but rather, potentiates IFNgamma-induced COX-2 expression in murine RAW264.7 macrophages. However, signal transducer and activator of transcription 1/3 (STAT1/3), known as a transcription factor on COX-2 expression, is inactivated by simvastatin in both cells. Our findings showed that simvastatin is likely to suppress IFNgamma-induced COX-2 expression by inhibiting STAT1/3 activation in human THP-1 cells, but not in murine RAW264.7 cells. Thus, we concluded that IFNgamma-induced COX-2 expression is differently regulated by simvastatin depending on species specific mechanism.
Language	eng
Pub Type(s)	Journal Article Research Support, Non-U.S. Gov't
PubMed ID	19886038

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