Simvastatin acts as an inhibitor of interferon gamma-induced cycloxygenase-2 expression in human THP-1 cells, but not in murine RAW264.7 cells

Abstract

Cyclooxygenase-2 (COX-2) is a key inflammatory response molecule,,in(] associated with Many immune functions of monocytes/macrophages. Particularly, interferon gamma (IFN gamma)-induced COX-2 expression appears in inflammatory conditions such as viral infection and autoimmune diseases. Recently statins have been reported to show variable effects oil COX-2 expression, and oil their cell and species type dependences. Based on the above description, we compared the effect of simvastatin on IFN gamma-induced COX-2 expression in human monocytes versus murine macrophages. In a result, we found that simvastatin suppresses IFN gamma-induced COX-2 expression in human THP-1 monocytes, but rather, potentiates IFN gamma-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 oil COX-2 expression, is inactivated by simvastatin in both cells. Our findings showed that simvastatin is likely to Suppress IFN gamma-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 IFN gamma-induced COX-2 expression is differently regulated by simvastatin depending oil species specific mechanism.