title: Upregulated expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in BALB/c mouse brain challenged with Japanese encephalitis virus.
abstract: BACKGROUND
  Uncontrolled immune responses in the nervous system are potentially damaging following Japanese encephalitis virus (JEV) infection. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) act together to control the proteolysis of extracellular matrix. Disbalances in the MMP/TIMP system during virally induced neurodegenerative processes and inflammations are responsive to changes in the progression of diseases.
  
  
  METHODS
  The expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-3 in JEV-infected mouse brain was analyzed by RT-PCR for semiquantitation and ELISA for estimation of protein along with brain histopathology at different days postinoculation (dpi). Gelatin gel zymography was performed for MMP-2 and MMP-9 activities.
  
  
  RESULTS
  In the virus-infected group, expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-3 was found to be increased from 1 dpi to 6 dpi as compared to controls by both RT-PCR and ELISA. The expressions of MMPs and TIMPs at mRNA and protein levels were in concordance with each other. Post hoc multiple comparison analysis between days revealed that, in the virus-infected groups, significant increases (p < 0.05) in MMP and TIMP levels were observed between various dpi at both mRNA and protein levels. Only the MMP-7 protein level at 6 dpi was not significant compared to 5 dpi (p = 0.99).
  
  
  CONCLUSIONS
  Overexpression of MMPs and TIMPs is associated with disease severity in the central nervous system (CNS) during JEV infection. Our results showed that JEV infection can alter the expression of MMPs and TIMPs in the CNS. Thus, assessing these important immune mediators in CNS infection appears to play an important role in the development of symptoms and may help to understand the JEV-induced neurological disorders. More studies are required on this important enzymatic system to study their role in immune mediated pathogenesis.
authors.affiliation: Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Vibha
authors.initials: V
authors.lastname: Shukla
authors.forename: Akhalesh
authors.initials: A
authors.lastname: Kumar Shakya
authors.forename: T N
authors.initials: TN
authors.lastname: Dhole
authors.forename: Usha Kant
authors.initials: UK
authors.lastname: Misra
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004664:Encephalitis Virus, Japanese / Q000378:metabolism*; D004672:Encephalitis, Japanese / Q000201:enzymology*; D005260:Female; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases