Inhibition of matrix metalloproteinases-2/-9 transiently reduces pre-oligodendrocyte loss during lipopolysaccharide-but not tumour necrosis factor-alpha-induced inflammation in fetal ovine glial culture

Weaver-Mikaere, Luke, Gunn, Alistair J., Bennet, Laura, Mitchell, Murray D. and Fraser, Mhoyra (2013) Inhibition of matrix metalloproteinases-2/-9 transiently reduces pre-oligodendrocyte loss during lipopolysaccharide-but not tumour necrosis factor-alpha-induced inflammation in fetal ovine glial culture. Developmental Neuroscience, 35 6: 461-473. doi:10.1159/000354862


Author Weaver-Mikaere, Luke
Gunn, Alistair J.
Bennet, Laura
Mitchell, Murray D.
Fraser, Mhoyra
Title Inhibition of matrix metalloproteinases-2/-9 transiently reduces pre-oligodendrocyte loss during lipopolysaccharide-but not tumour necrosis factor-alpha-induced inflammation in fetal ovine glial culture
Journal name Developmental Neuroscience   Check publisher's open access policy
ISSN 0378-5866
1421-9859
Publication date 2013-12-01
Year available 2013
Sub-type Article (original research)
DOI 10.1159/000354862
Open Access Status Not Open Access
Volume 35
Issue 6
Start page 461
End page 473
Total pages 13
Place of publication Basel, Switzerland
Publisher S. Karger AG
Language eng
Abstract To determine whether increased matrix metalloproteinase (MMP) proteolytic activity plays a pathological role in infection/inflammation-induced preterm brain injury, primary cultures of preterm (day 90 of gestation; term 145 days) fetal ovine mixed glia were exposed to 24-96 h of lipopolysaccharide (LPS, 1 μg/ml) or tumour necrosis factor-α (TNF-α, 100 ng/ml). MMP-2 mRNA levels were significantly increased after TNF-α (96 h) and LPS exposure (48 and 96 h), and MMP-9 mRNA levels were significantly increased at 48 and 96 h after TNF-α. On zymography, the active form of secreted MMP-2 was significantly increased 24 h after LPS, but not TNF-α. Both active and latent forms of MMP-9 gelatinolytic activity were significantly increased by TNF-α (96 h) and LPS (72 and 96 h). On reverse zymography, inhibitory activity of TIMP-1 but not TIMP-2 was significantly increased by TNF-α and LPS. SB-3CT-mediated MMP-2 and MMP-9 inhibition transiently reduced LPS-induced oligodendrocyte cell death but had no effect during TNF-α exposure. Collectively, these observations suggest a limited, transient effect of MMPs on immature white matter damage associated with infection but not TNF-α-mediated inflammation.
Keyword Cell death
Fetal sheep
Glia
In vitro study
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
 
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