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. 2008;14(3):205–217. doi: 10.1080/13550280802008305

Differential transcription of matrix-metalloproteinase genes in primary mouse astrocytes and microglia infected with Theiler’s murine encephalomyelitis virus

Jirawat Kumnok 1, Reiner Ulrich 1, Konstantin Wewetzer 1,2, Karl Rohn 3, Florian Hansmann 1, Wolfgang Baumgärtner 1,✉, Susanne Alldinger 1
PMCID: PMC7095224  PMID: 18569455

Abstract

The BeAn strain of Theiler’s murine encephalomyelitis virus (TMEV) induces demyelinating disease in susceptible mice comparable to human multiple sclerosis. Recent in vivo studies showed that matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of MMPs, TIMPs) are associated with demyelination in Theiler’s murine encephalomyelitis. The present study was performed to evaluate the in vitro MMP and TIMP expression in astrocytes and microglia following TMEV infection. Brain cell cultures from SJL/J mice were infected with the BeAn strain of TMEV and the expressions of 11 MMPs and 4 TIMPs were evaluated by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) at different time points post infection (p.i.). In control astrocytes and microglia, a constitutive expression of MMP-2, -3, -9, -10, -12, -13,-14, -15, -24 and TIMP-2 to -4 was detected. In addition, TIMP-1 and MMP-11 was found in astrocytes only, and MMP-7 was absent in both cells cultures. RT-qPCR demonstrated high virus RNA copy numbers in astrocytes and a low amount in microglia. In accordance, TMEV antigen was detected in astrocytes, whereas it was below the limit of detection in microglia. MMP-3, -9, -10, -12, and -13 as well as TIMP-1 were the enzymes most prominently up-regulated in TMEV-infected astrocytes. In contrast, TMEV infection was associated with a down-regulation of MMPs and TIMPs in microglia. Conclusively, in addition to inflammatory infiltrates, TMEV-induced astrocytic MMPs might trigger a proteolysis cascade leading to an opening of the blood-brain barrier and demyelination in vivo.

Keywords: brain cell culture, mouse, MMPs, TIMPs, TMEV

Footnotes

Jirawat Kumnok and Reiner Ulrich contributed equally to this work.

This article is in memory of Jirawat Kumnok, a young outstanding scientist who passed away far too early.

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