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1.
Biocell ; Biocell;33(2): 107-114, Aug. 2009. tab, graf
Article in English | BINACIS | ID: bin-127208

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 transcriptio n 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.(AU)


Subject(s)
Humans , Animals , Mice , B7-2 Antigen/genetics , B7-2 Antigen/metabolism , Macrophages , Macrophages/enzymology , Monocytes , Monocytes/enzymology , RNA, Messenger/genetics , RNA, Messenger/metabolism , STAT1 Transcription Factor/metabolism , STAT3 Transcription Factor/metabolism , Cyclooxygenase 2/metabolism , Interferon-gamma/pharmacology , Simvastatin/pharmacology
2.
Biocell ; Biocell;33(2): 107-114, Aug. 2009. tab, graf
Article in English | LILACS | ID: lil-595035

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 transcriptio n 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.


Subject(s)
Humans , Animals , Mice , RNA, Messenger/genetics , RNA, Messenger/metabolism , /genetics , /metabolism , Macrophages , Macrophages/enzymology , Monocytes , Monocytes/enzymology , /metabolism , STAT1 Transcription Factor/metabolism , /metabolism , Interferon-gamma/pharmacology , Simvastatin/pharmacology
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