title: Induction of matrix metalloproteinase-2 and -9 via Erk1/2-NF-κB pathway in human astroglia infected with Toxoplasma gondii.
abstract: Matrix metalloproteinase (MMP)-2 and MMP-9 can cleave fibronectin, allowing leukocyte migration to the site of Toxoplasma gondii infection during toxoplasmic encephalitis. The aim of this study was to investigate the association between extracellular signal-regulated kinase (Erk)1/2-nuclear factor (NF)-κB pathway and MMP-2/-9 expression in astroglia infected with T. gondii tachyzoite in vitro. Our results showed that phosphorylated (p)-Erk1/2 transiently increased 1h post-infection (PI) and p-NF-κB significantly increased from 1h PI to 12h PI in cell homogenates. NF-κB was bound directly to oligonucleotides containing putative NF-κB binding sites for the MMP-9 promoter. Additionally, expression of p-NF-κB, MMP-2, and MMP-9 was significantly decreased by MG132, an indirect NF-κB inhibitor. Treatment with PD98059, an Erk kinase inhibitor, efficiently reduced p-Erk1/2, p-NF-κB, MMP-2, and MMP-9 expression. These results suggest that suppression of the Erk1/2-NF-κB signaling pathway causes reductions in MMP-2 and MMP-9 activities in astroglia response to T. gondii infection. Thus, inhibiting this signaling intermediate involved in MMP-2 and MMP-9 expression may be a potential method for controlling inflammatory development of T. gondii-induced encephalitis.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: Cheng-You
authors.initials: CY
authors.lastname: Lu
authors.forename: Shih-Chan
authors.initials: SC
authors.lastname: Lai
mesh_terms: D001253:Astrocytes / Q000378:metabolism*; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000469:parasitology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007976:Leupeptins; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014122:Toxoplasma / Q000502:physiology*
chemical_list: D007976:Leupeptins; D016328:NF-kappa B; D048049:Extracellular Signal-Regulated MAP Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde