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A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1
- Source :
- BMC Immunology, Vol 10, Iss 1, p 64 (2009)
- Publication Year :
- 2009
- Publisher :
- BMC, 2009.
-
Abstract
- Abstract Background Mycobacterium tuberculosis (MTB) is a major cause of morbidity and mortality in the world. To combat against this pathogen, immune cells release cytokines including tumor necrosis factor-α (TNF-α), which is pivotal in the development of protective granulomas. Our previous results showed that Bacillus Calmette Guerin (BCG), a mycobacterium used as a model to investigate the immune response against MTB, stimulates the induction of TNF-α via mitogen-activated protein kinase (MAPK) in human blood monocytes. Since MAPK phosphatase-1 (MKP-1) is known to regulate MAPK activities, we examined whether MKP-1 plays a role in BCG-induced MAPK activation and cytokine expression. Results Primary human blood monocytes were treated with BCG and assayed for MKP-1 expression. Our results demonstrated that following exposure to BCG, there was an increase in the expression of MKP-1. Additionally, the induction of MKP-1 was regulated by p38 MAPK and extracellular signal-regulated kinase 1 and 2 (ERK1/2). Surprisingly, when MKP-1 expression was blocked by its specific siRNA, there was a significant decrease in the levels of phospho-MAPK (p38 MAPK and ERK1/2) and TNF-α inducible by BCG. Conclusions Since TNF-α is pivotal in granuloma formation, the results indicated an unexpected positive function of MKP-1 against mycobacterial infection as opposed to its usual phosphatase activity.
- Subjects :
- Immunologic diseases. Allergy
RC581-607
Subjects
Details
- Language :
- English
- ISSN :
- 14712172
- Volume :
- 10
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- BMC Immunology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.bcca9e55c75445e2bdc19ee43317e630
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/1471-2172-10-64