Activation of JAK2/STAT1-alpha-dependent signaling events during Mycobacterium tuberculosis-induced macrophage apoptosis.

Abstract	Induction of apoptosis by Mycobacterium tuberculosis in murine macrophage involves TNF-alpha and nitric oxide (NO) production and caspase cascade activation; however, the intracellular signaling pathways implicated remain to be established. Our results indicate that infection of the B10R murine macrophage line with M. tuberculosis induces apoptosis independent of mycobacterial phagocytosis and that M. tuberculosis induces protein tyrosine kinase (PTK) activity, JAK2/STAT1-alpha phosphorylation, and STAT1-alpha nuclear translocation. Inhibitors of PTK (AG-126), or JAK2 (AG-490) inhibited TNF-alpha and NO production, caspase 1 activation and apoptosis, suggesting that M. tuberculosis-induction of these events depends on JAK2/STAT1-alpha activation. In addition, we have obtained evidence that ManLAM capacity to inhibit M. tuberculosis-induced apoptosis involves the activation of the PTP SHP-1. The finding that M. tuberculosis infection activate JAK2/STAT1-alpha pathway suggests that M. tuberculosis might mimic macrophage-activating stimuli.
Authors	Mauricio Rojas, Martin Olivier, Luis F García
Journal	Cellular immunology (Cell Immunol) 2002 May-Jun Vol. 217 Issue 1-2 Pg. 58-66 ISSN: 0008-8749 [Print] Netherlands
PMID	12426001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Enzyme Inhibitors Interferon-Stimulated Gene Factor 3 Proto-Oncogene Proteins Transcription Factors Tumor Necrosis Factor-alpha gamma interferon activation factor Nitric Oxide Protein-Tyrosine Kinases Jak2 protein, mouse Janus Kinase 2 Caspases
Topics	Active Transport, Cell Nucleus Animals Apoptosis Caspases (metabolism) Cell Line Cell Nucleus (metabolism) Enzyme Activation Enzyme Inhibitors (pharmacology) Interferon-Stimulated Gene Factor 3 Janus Kinase 2 Macrophages (immunology, microbiology) Mice Mice, Inbred C3H Mycobacterium tuberculosis (pathogenicity) Nitric Oxide (biosynthesis) Phagocytosis Phosphorylation Protein-Tyrosine Kinases (antagonists & inhibitors, metabolism) Proto-Oncogene Proteins Signal Transduction Transcription Factors (metabolism) Tumor Necrosis Factor-alpha (biosynthesis)

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