Please use this identifier to cite or link to this item:
https://doi.org/10.1186/1742-2094-8-46
DC Field | Value | |
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dc.title | Mycobacterium tuberculosis-infected human monocytes down-regulate microglial MMP-2 secretion in CNS tuberculosis via TNF?, NF?B, p38 and caspase 8 dependent pathways | |
dc.contributor.author | Green, J.A | |
dc.contributor.author | Dholakia, S | |
dc.contributor.author | Janczar, K | |
dc.contributor.author | Ong, C.W.M | |
dc.contributor.author | Moores, R | |
dc.contributor.author | Fry, J | |
dc.contributor.author | Elkington, P.T | |
dc.contributor.author | Roncaroli, F | |
dc.contributor.author | Friedland, J.S | |
dc.date.accessioned | 2020-10-20T08:13:45Z | |
dc.date.available | 2020-10-20T08:13:45Z | |
dc.date.issued | 2011 | |
dc.identifier.citation | Green, J.A, Dholakia, S, Janczar, K, Ong, C.W.M, Moores, R, Fry, J, Elkington, P.T, Roncaroli, F, Friedland, J.S (2011). Mycobacterium tuberculosis-infected human monocytes down-regulate microglial MMP-2 secretion in CNS tuberculosis via TNF?, NF?B, p38 and caspase 8 dependent pathways. Journal of Neuroinflammation 8 : 46. ScholarBank@NUS Repository. https://doi.org/10.1186/1742-2094-8-46 | |
dc.identifier.issn | 1742-2094 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/178177 | |
dc.description.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-?. 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 NF?B 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 NF?B pathways; p38 phosphorylation was increased and p50/p65 NF?B 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-?, p38 MAP kinase and NF?B in addition to a novel caspase 8-dependent pathway. © 2011 Green et al; licensee BioMed Central Ltd. | |
dc.publisher | BMC | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | caspase 8 | |
dc.subject | gelatinase A | |
dc.subject | immunoglobulin enhancer binding protein | |
dc.subject | mitogen activated protein kinase p38 | |
dc.subject | transcription factor RelA | |
dc.subject | tumor necrosis factor alpha | |
dc.subject | caspase 8 | |
dc.subject | gelatinase A | |
dc.subject | helenalin | |
dc.subject | immunoglobulin enhancer binding protein | |
dc.subject | mitogen activated protein kinase | |
dc.subject | mitogen activated protein kinase p38 | |
dc.subject | nonsteroid antiinflammatory agent | |
dc.subject | sesquiterpene | |
dc.subject | tumor necrosis factor alpha | |
dc.subject | article | |
dc.subject | brain biopsy | |
dc.subject | central nervous system tuberculosis | |
dc.subject | clinical article | |
dc.subject | controlled study | |
dc.subject | down regulation | |
dc.subject | enzyme inhibition | |
dc.subject | enzyme regulation | |
dc.subject | enzyme release | |
dc.subject | gene expression | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | human tissue | |
dc.subject | macrophage | |
dc.subject | microglia | |
dc.subject | monocyte | |
dc.subject | Mycobacterium tuberculosis | |
dc.subject | nonhuman | |
dc.subject | chemistry | |
dc.subject | culture medium | |
dc.subject | cytology | |
dc.subject | genetics | |
dc.subject | metabolism | |
dc.subject | microbiology | |
dc.subject | microglia | |
dc.subject | Mycobacterium tuberculosis | |
dc.subject | pathogenicity | |
dc.subject | physiology | |
dc.subject | secretion | |
dc.subject | signal transduction | |
dc.subject | Anti-Inflammatory Agents, Non-Steroidal | |
dc.subject | Caspase 8 | |
dc.subject | Culture Media, Conditioned | |
dc.subject | Extracellular Signal-Regulated MAP Kinases | |
dc.subject | Humans | |
dc.subject | Matrix Metalloproteinase 2 | |
dc.subject | Microglia | |
dc.subject | Monocytes | |
dc.subject | Mycobacterium tuberculosis | |
dc.subject | NF-kappa B | |
dc.subject | p38 Mitogen-Activated Protein Kinases | |
dc.subject | Sesquiterpenes | |
dc.subject | Signal Transduction | |
dc.subject | Tuberculosis, Central Nervous System | |
dc.subject | Tumor Necrosis Factor-alpha | |
dc.type | Article | |
dc.contributor.department | DEPT OF MEDICINE | |
dc.description.doi | 10.1186/1742-2094-8-46 | |
dc.description.sourcetitle | Journal of Neuroinflammation | |
dc.description.volume | 8 | |
dc.description.page | 46 | |
dc.published.state | published | |
Appears in Collections: | Staff Publications Elements |
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