REGULATION OF MATRIXMETALLOPROTEINASE (MMP)-2, MMP-9 AND TISSUE INHIBITOR OF METALLOPROTEINASE (TIMP)-1, TIMP-2 EXPRESSION BY [6]-GINGEROL IN DENGUE VIRUS INFECTED CELL

Abstract

The role of matrixmetalloproteinase (MMP)-2 and MMP-9 in vascular leakage associated with dengue haemorrhagic fever and MMPs regulation by tissue inhibitor of metalloproteinases (TIMPs) has been established. Control of MMPs and TIMPs activity is of great significance to prevent vascular leakage caused by dengue virus (DV) infection. Gingerol (Zingiber officinale Roscoe, Zingiberaceae) is one of the most frequently and heavily consumed dietary condiments throughout the world. This study evaluates the effect of [6] -gingerol on the expression profile of MMP-2, MMP-9 and their tissue inhibitors TIMP-1, TIMP-2 at the MRNA level in DV infected Vero cells. Using quantitative real time RT-PCR, we demonstrated that [6]-gingerol significantly downregulated the mRNA expression of MMP-2 and MMP-9, whereas upregulated the expression of TIMP-1 and TIMP-2 in DV infected cells in a concentration-and time-dependent manner. At high concentrations of [6]-gingerol, TIMP-1 and TIMP-2 were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of MMP-2 and MMP-9 mRNA expression levels. These results suggest that [6] -gingerol may play a role in regulating vascular leakage by modulating expression of MMP-2, MMP-9 and TIMP-1, TIMP-2 in dengue virus infected cells. Therefore, therapeutic strategies utilizing [6] -gingerol could be developed to substantially reduce dengue morbidity and mortality.