Please use this identifier to cite or link to this item: https://doi.org/10.1186/1742-2094-8-46
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
Authors: Green, J.A
Dholakia, S
Janczar, K
Ong, C.W.M 
Moores, R
Fry, J
Elkington, P.T
Roncaroli, F
Friedland, J.S
Keywords: caspase 8
gelatinase A
immunoglobulin enhancer binding protein
mitogen activated protein kinase p38
transcription factor RelA
tumor necrosis factor alpha
caspase 8
gelatinase A
helenalin
immunoglobulin enhancer binding protein
mitogen activated protein kinase
mitogen activated protein kinase p38
nonsteroid antiinflammatory agent
sesquiterpene
tumor necrosis factor alpha
article
brain biopsy
central nervous system tuberculosis
clinical article
controlled study
down regulation
enzyme inhibition
enzyme regulation
enzyme release
gene expression
human
human cell
human tissue
macrophage
microglia
monocyte
Mycobacterium tuberculosis
nonhuman
chemistry
culture medium
cytology
genetics
metabolism
microbiology
microglia
Mycobacterium tuberculosis
pathogenicity
physiology
secretion
signal transduction
Anti-Inflammatory Agents, Non-Steroidal
Caspase 8
Culture Media, Conditioned
Extracellular Signal-Regulated MAP Kinases
Humans
Matrix Metalloproteinase 2
Microglia
Monocytes
Mycobacterium tuberculosis
NF-kappa B
p38 Mitogen-Activated Protein Kinases
Sesquiterpenes
Signal Transduction
Tuberculosis, Central Nervous System
Tumor Necrosis Factor-alpha
Issue Date: 2011
Publisher: BMC
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
Rights: Attribution 4.0 International
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.
Source Title: Journal of Neuroinflammation
URI: https://scholarbank.nus.edu.sg/handle/10635/178177
ISSN: 1742-2094
DOI: 10.1186/1742-2094-8-46
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1186_1742-2094-8-46.pdf1.26 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

23
checked on May 12, 2022

Page view(s)

117
checked on May 12, 2022

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons