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

CHANG SEOK LEE1, YONG JAE SHIN1, CHEOLHEE WON1, YUN-SONG LEE2, CHUNG-GYU PARK3, SANG-KYU YE1*, MYUNG-HEE CHUNG1
1. Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea.
2. Department of Pharmacology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
3. Department of Microbiology, Seoul National University College of Medicine, Seoul 110-799, Korea.
* Address correspondence to: Sang-Kyu Ye. E-mail: sangkyu@snu.ac.kr

BIOCELL 2009, 33(2), 107-114. https://doi.org/10.32604/biocell.2009.33.107

Abstract

Cyclooxygenase-2 (COX-2) is a key inflammatory response molecule, and associated with many immune functions of monocytes/macrophages. Particularly, interferon gamma (IFNγ)-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 IFNγ-induced COX2 expression in human monocytes versus murine macrophages. In a result, we found that simvastatin suppresses IFNγ-induced COX-2 expression in human THP-1 monocytes, but rather, potentiates IFNγ-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 IFNγ-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 IFNγ-induced COX-2 expression is differently regulated by simvastatin depending on species specific mechanism.

Keywords

monocyte, macrophage, INFγ, STAT1/3, SOCS1/3

Cite This Article

LEE, C. S., SHIN, Y. J., WON, C., LEE, Y., PARK, C. et al. (2009). 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, 33(2), 107–114.

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This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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