title: Up-regulation of matrix metalloproteinases-2 and -9 via an Erk1/2/NF-κB pathway in murine mast cells infected with Toxoplasma gondii.
abstract: Mast cells are key effectors in inflammation and contain proteinases that are released on activation. This study investigates associations between extracellular signal-regulated kinase (Erk)1/2, nuclear factor (NF)-κB, matrix metalloproteinase (MMP)-2 and MMP-9 in mast cells infected with Toxoplasma gondii tachyzoites. T. gondii infection led to increased mast cell degranulation. Phosphorylated (p)-Erk1/2 and p-NF-κB were increased significantly in mast cells infected with T. gondii. Pretreatment with the Erk kinase inhibitor PD98059 significantly decreased the expression of p-Erk1/2, p-NF-κB, MMP-2 and MMP-9. Treatment with MG132, an indirect NF-κB inhibitor, effectively reduced p-IκBα, p-NF-κB, MMP-2 and MMP-9 expression. Collectively, these data show that suppression of an Erk1/2/NF-κB signalling pathway caused a reduction in MMP-2 and -9 activities. Inhibiting this signalling pathway for MMP-2 and MMP-9 expression might offer a potential way to control early T. gondii infection. This pathway for the generation of MMP-2 and MMP-9 is important for mast cell secretion and the NF-κB/Erk1/2 signalling pathway may be key in MMP-2 and MMP-9 production in host defense against toxoplasmosis.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: M-F
authors.initials: MF
authors.lastname: Wang
authors.forename: C-Y
authors.initials: CY
authors.lastname: Lu
authors.forename: S-C
authors.initials: SC
authors.lastname: Lai
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D020935:MAP Kinase Signaling System / Q000276:immunology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014123:Toxoplasmosis / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016328:NF-kappa B; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9
keywords: Erk1/2; MMP-2; MMP-9; NF-κB; Toxoplasma gondii