Email updates

Keep up to date with the latest news and content from BMC Immunology and BioMed Central.

Open Access Highly Accessed Research article

A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1

Benny KW Cheung, Howard CH Yim, Norris CM Lee and Allan SY Lau*

Author Affiliations

Cytokine Biology Group, Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, PR China

For all author emails, please log on.

BMC Immunology 2009, 10:64  doi:10.1186/1471-2172-10-64

Published: 17 December 2009

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.