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Mycobacterium tuberculosis -infected human monocytes down-regulate microglial MMP-2 secretion in CNS tuberculosis via TNFα, NFκB, p38 and caspase 8 dependent pathways by Justin A Green; Shruti Dholakia; Karolina Janczar; Catherine WM Ong; Rachel Moores; Julie Fry; Paul T Elkington; Federico Roncaroli; Jon S Friedland is a Neuroscience article available to read on EtoBox.

What is Mycobacterium tuberculosis -infected human monocytes down-regulate microglial MMP-2 secretion in CNS tuberculosis via TNFα, NFκB, p38 and caspase 8 dependent pathways about?

Tuberculosis (TB) of the central nervous system (CNS) is a deadly disease characterized by extensive tissue destruction, driven by molecules such as Matrix Metalloproteinase-2 (MMP-2) which targets CNS-specific substrates. In a simplified cellular model of CNS TB, we demonstrated that conditioned medium from __Mycobacterium tuberculosis__-infected primary human monocytes (CoMTb), but not direct infection, unexpectedly down-regulates constitutive microglial MMP-2 gene expression and secretion by 72.8% at 24 hours, sustained up to 96 hours (P < 0.01), dependent upon TNF-α. In human CNS TB brain biopsies but not controls the p38 pathway was activated in microglia/macrophages. Inhibition of the p38 MAP kinase pathway resulted in a 228% increase in MMP-2 secretion (P < 0.01). In contrast ERK MAP kinase inhibition further decreased MMP-2 secretion by 76.6% (P < 0.05). Inhibition of the NFκB pathway resulted in 301% higher MMP-2 secretion than CoMTb alone (P < 0.01). Caspase 8 restored MMP-2 secretion to basal levels. However, this caspase-dependent regulation of MMP-2 was independent of p38 and NFκB pathways; p38 phosphorylation was increased and p50/p65 NFκB nuclear trafficking unaffect

Who reads Mycobacterium tuberculosis -infected human monocytes down-regulate microglial MMP-2 secretion in CNS tuberculosis via TNFα, NFκB, p38 and caspase 8 dependent pathways?

Author

Justin A Green; Shruti Dholakia; Karolina Janczar; Catherine WM Ong; Rachel Moores; Julie Fry; Paul T Elkington; Federico Roncaroli; Jon S Friedland

Publisher

BioMed Central; Springer (Biomed Central Ltd.); [London]: BioMed Central, c2004-; Springer Science and Business Media LLC; Society for Mining, Metallurgy and Exploration Inc. (ISSN 1742-2094)

Published

2011

Language

EN

Field

Neuroscience (Life Sciences)