Article ID: JJID.2013.481
Disease severities following Dengue virus (DV) infection are caused by increased vascular permeability leading to hypovolemic shock. Matrix metalloproteinases (MMPs) are believed to play a key role in promoting such severities. A previous study reported that supernatants of DV-infected DCs which contained overproduction of MMP-2 and MMP-9 induced vascular leakage in a mouse model. In the present work, we investigated whether hepatocytes (HepG2) and monocytes (U937) could be additional sources of MMPs during DV infection. HepG2 and U937 cells were exposed to DV 2 strain 16681. The secretion of MMP-2 and MMP-9 were detected using gelatin zymography. We found that DV-infected HepG2 increased the levels of MMP-2 while infected U937 cells promoted MMP-9 production. Semi-quantitative RT-PCR results also confirmed that DV-infected HepG2 cells up-regulated the expression of MMP-2 mRNA whereas infected U937 cells enhanced that of MMP-9 mRNA. We monitored the expression of endogenous TIMP-1 and TIMP-2. DV infection induced TIMP-1 expression in U937 cells. However, lower expression of TIMP-2 was observed in infected HepG2 cells. We believed that following DV infection, monocytes and hepatocytes can act as MMP-9 and MMP-2 producers, respectively. Their responses could be attributed to the disturbance of TIMPs expression by DV in different cell types.
