Up-regulation of Matrix Metalloproteinases-2 and -9 via an Erk1/2/NF-κB Pathway in Murine Mast Cells Infected with Toxoplasma gondii

J Comp Pathol. 2013 May 7. pii: S0021-9975(13)00051-0. doi: 10.1016/j.jcpa.2013.03.002. [Epub ahead of print]

Up-regulation of Matrix Metalloproteinases-2 and -9 via an Erk1/2/NF-κB Pathway in Murine Mast Cells Infected with Toxoplasma gondii

Wang MF, Lu CY, Lai SC.

Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Department of Pediatrics, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan

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.

PMID: 23664424 [PubMed - as supplied by publisher]