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.
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.
authors.affiliation: The Liggins Institute, Auckland, New Zealand.
authors.forename: Luke
authors.initials: L
authors.lastname: Weaver-Mikaere
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Gunn
authors.forename: Laura
authors.initials: L
authors.lastname: Bennet
authors.forename: Murray D
authors.initials: MD
authors.lastname: Mitchell
authors.forename: Mhoyra
authors.initials: M
authors.lastname: Fraser
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9