ArticleJournal of neuroinflammation2011
Mycobacterium tuberculosis-infected human monocytes down-regulate microglial MMP-2 secretion in CNS tuberculosis via TNFα, NFκB, p38 and caspase 8 dependent pathways.
Article in Journal of neuroinflammation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Ischaemia in tuberculous meningitis: update on pathophysiology, clinical predictors and management.Current opinion in infectious diseases · 2026Review
- The potential role and value of vitamin D in the treatment of tuberculosis.Frontiers in cellular and infection microbiology · 2025Review
- Physiological stage-dependent effects ofFrontiers in microbiology · 2025Article
- Article
- Maternal dietary deficiency in choline reduced levels of MMP-2 levels in blood and brain tissue of male offspring mice.bioRxiv : the preprint server for biology · 2024Article
- Article
- The role of purinergic receptors in neural repair and regeneration after spinal cord injury.Neural regeneration research · 2023Review
- Effect of Systemic Inflammation in the CNS: A Silent History of Neuronal Damage.International journal of molecular sciences · 2023Review
- Recent advances in understanding the human host immune response in tuberculous meningitis.Frontiers in immunology · 2023Review
- Gliosis, misfolded protein aggregation, and neuronal loss in a guinea pig model of pulmonary tuberculosis.Frontiers in neuroscience · 2023Article
- Nos2Journal of neuroinflammation · 2022Article
- Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children.Pathogens (Basel, Switzerland) · 2021Article
- Neutrophil-Mediated Immunopathology and Matrix Metalloproteinases in Central Nervous System - Tuberculosis.Frontiers in immunology · 2021Review
- Article
- The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity: Focus on Sicilian Long-Living Individuals (LLIs).Mediators of inflammation · 2020Article
- Matrix Metalloproteinases in Pulmonary and Central Nervous System Tuberculosis-A Review.International journal of molecular sciences · 2019Review
- Complex regulation of neutrophil-derived MMP-9 secretion in central nervous system tuberculosis.Journal of neuroinflammation · 2017Article
- Early Secretory Antigenic Target-6 Drives Matrix Metalloproteinase-10 Gene Expression and Secretion in Tuberculosis.American journal of respiratory cell and molecular biology · 2017Article
- Hypoxia and tissue destruction in pulmonary TB.Thorax · 2016Article
- Microglia activation in a pediatric rabbit model of tuberculous meningitis.Disease models & mechanisms · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
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 unaffected by caspase 8 inhibition. In summary, suppression of microglial MMP-2 secretion by M.tb-infected monocyte-dependent networks paradoxically involves the pro-inflammatory mediators TNF-α, p38 MAP kinase and NFκB in addition to a novel caspase 8-dependent pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.