Tuberc Respir Dis.  2012 Mar;72(3):275-283.

Impaired Expression of MAPK Is Associated with the Downregulation of TNF-alpha, IL-6, and IL-10 in Mycobacterium abscessus Lung Disease

• Sim YS
• Kim SY
• Kim EJ
• Shin SJ
• Koh WJ

Abstract

BACKGROUND
Healthy individuals who develop nontuberculous mycobacteria (NTM) lung disease are likely to have specific susceptibility factors which can lead to a NTM infection. The aim of the present study was to investigate the mechanism underlying innate immune responses, including the role of mitogen-activated protein kinase (MAPK), in Mycobacterium abscessus lung disease.
METHODS
Extracellular signal-regulated kinase (ERK1/2) and p38 MAPK expression in monocytes from peripheral blood mononuclear cells were measured by Western blot analysis after stimulation by Mycobacterium avium in five patients with M. abscessus lung disease and seven healthy controls. A M. avium-induced cytokine assay was performed after inhibition of ERK1/2 and p38 MAPK pathways.
RESULTS
Mycobacterium avium induced p38 and ERK1/2 expression in monocytes from healthy controls and subsequently upregulated tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 production. In monocytes from patients with M. abscessus lung disease, however, induction of p38 and ERK1/2 expression, and the production of TNF-alpha, IL-6, and IL-10 were significantly lower.
CONCLUSION
Decreased activity of MAPK and cytokine secretion in monocytes from patients with M. abscessus lung disease may provide an explanation regarding host susceptibility to these uncommon infections.

Keyword

Nontuberculous Mycobacteria; Extracellular Signal-Regulated MAP Kinases; Mitogen-Activated Protein Kinases

MeSH Terms

Blotting, Western
Down-Regulation
Extracellular Signal-Regulated MAP Kinases
Humans
Immunity, Innate
Interleukin-10
Interleukin-6
Interleukins
Lung
Lung Diseases
Mitogen-Activated Protein Kinases
Monocytes
Mycobacterium
Mycobacterium avium
Nontuberculous Mycobacteria
p38 Mitogen-Activated Protein Kinases
Phosphotransferases
Protein Kinases
Tumor Necrosis Factor-alpha
Extracellular Signal-Regulated MAP Kinases
Interleukin-10
Interleukin-6
Interleukins
Mitogen-Activated Protein Kinases
Phosphotransferases
Protein Kinases
Tumor Necrosis Factor-alpha
p38 Mitogen-Activated Protein Kinases

Figure

• 

  Figure 1 Mycobacterium avium-induced extracellular signal-regulated kinase (ERK1/2) and p38 expression in peripheral blood monocytes from patients with M. abscessus lung disease and healthy controls. ERK1/2 (A) and p38 (B) activation with M. avium or lipoteichoic acid (LTA) significantly decreased in patients (gray bar) as compared to healthy controls (white bar). Expression of ERK1/2 and p38 via inhibition with the anti-TLR2 antibody were not different between patients and controls. *p<0.05. †p<0.01. TLR2 Ab: Toll-like receptor 2 antibody.

• 

  Figure 2 (A~C) Inhibitory effects of extracellular signal-regulated kinase (ERK1/2) and p38 on Mycobacterium avium-induced tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in monocytes from patients with M. abscessus lung disease and healthy controls. The anti-TLR2-specific antibody, the p38 signaling inhibitor SB203580 (SB), or the ERK1/2 selective inhibitor PD98059 (PD) prior to infection with M. avium at a MOI of 70 was added to the cells. The supernatants were harvested and ELISA was used to measure cytokine activity. *p<0.05. †p<0.01. TLR2 Ab: toll-like receptor 2 antibody; MOI: multiplicity of infection; ELISA: enzyme-linked immunosorbent assays; controls: white bar; patients: gray bar.

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