Matrix metalloproteinases and their tissue inhibitors in serum and cerebrospinal fluid of children with Japanese encephalitis virus infection

Abstract

The expression of matrix metalloproteinases (MMPs) is tightly regulated at the level of gene transcription, conversion of pro-enzyme to active MMPs, and the action of tissue inhibitors of metalloproteinases (TIMPs). The present study aimed to investigate the expression of some specific MMPs (2, 7, 9) and TIMPs (1, 2, 3) in serum and cerebrospinal fluid (CSF) of children with Japanese encephalitis virus (JEV) infection. Serum and CSF levels of MMPs and TIMPs in children with JEV infection and disease control (DC) were compared. The CSF and serum concentrations of MMP-2, TIMP-2 and TIMP-3 were significantly higher in children with JEV infection compared to DC. The concentration of MMP-9 in serum was significantly higher in children with JEV infection than in the DC and healthy control (HC), while in the CSF, no significant difference was observed compared to DC. The MMP-7 serum concentration was significantly higher in children with JEV infection compared to HC, but no significant difference was observed compared to DC. MMP-7 concentration was undetectable in CSF in both groups. The TIMP-1 CSF concentration was significantly higher, while the serum concentration was significantly lower, in children with JEV infection compared to DC. No correlation was found between the levels of each biomolecule measured in CSF and serum, suggesting that the levels in CSF represent local production within the CNS rather than production in the periphery. We also observed leucocytosis, mononuclear pleocytosis and elevated protein concentrations in the CSF of children with JEV infection compared to DC.