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Biochemistry (Moscow)

, 76:938 | Cite as

Mitogen-activated protein kinases mediate the production of B-cell lymphoma 2 protein by Mycobacterium tuberculosis in Monocytes

  • P. L. Natarajan
  • Sujatha NarayananEmail author
Article

Abstract

Changes in the levels of antiapoptotic protein B-cell lymphoma 2 (Bcl-2) protein has been reported in murine and human tuberculosis. We investigated the role of mitogen-activated protein kinase pathways in the production of Bcl-2 protein in THP-1 human monocytes infected with Mycobacterium tuberculosis H37Rv and H37Ra. Analysis of phosphorylation profiles of mitogen-activated protein kinase kinase-1, extracellular-signal regulated kinase 1/2, mitogen-activated protein kinase kinase 3/6, and p38 mitogen-activated protein kinase; B-cell lymphoma 2 kinetics; and tumor necrosis factor-α (TNF-α) secretion levels showed variation between the two strains. Mycobacterium tuberculosis H37Rv induced higher Bcl-2 and lower TNF-α levels, whereas H37Ra the reverse. The strains also differed in their usage of CD14 and human leukocyte antigen-DR receptors in mediating extracellular-signal regulated kinase 1/2 and p38 mitogen-activated protein kinase activation. Mycobacterium tuberculosis H37Rv- and H37Ra-induced Bcl-2 production was reduced by specific inhibitors of mitogen-activated protein kinase kinase-1 (PD98059) and p38 (SB203580), but increased by nuclear factor κB (NF-κB) inhibitor (BAY 11-7082). TNF-α production by both strains was reduced in the presence of specific inhibitors of mitogen-activated protein kinase kinase-1 (PD98059), p38 (SB203580), and NF-κB (BAY 11-7082). Furthermore, inhibition of NF-κB was accompanied by an increase in strain-induced extracellular-signal regulated kinase 1/2 phosphorylation. Collectively, these results indicate for the first time that the production of Bcl-2 and TNF-α by M. tuberculosis H37Rv/H37Ra-infected THP-1 human monocytes is mediated through mitogen-activated protein kinases and NF-κB.

Key words

M. tuberculosis ERK p38 MAPK Bcl-2 production NF-κB 

Abbreviations

ANOVA

analysis of variance

AP-1

activator protein-1

BCG

bacillus Calmette-Guerin

CR

complement receptor

CREB

cAMP-response element-binding protein

DMSO

dimethylsulfoxide

ELISA

enzyme linked immunosorbent assay

ERK

extracellular signal regulated kinase

FCS

fetal calf serum

H37Ra

M. tuberculosis H37Ra

H37Rv

M. tuberculosis H37Rv

JNK or SAPK

c-jun N-terminal kinases or stress-activated protein kinase

LPS

lipopolysaccharide

MAPK

mitogen-activated protein kinase

MEK

mitogen-activated protein kinase kinase

MKK or MAPKK or MEK

MAPK kinases

MKP-1

MAPK phosphatase-1

NF-κB

nuclear factor κB

PBS

phosphate-buffered saline

PD98059

MEK inhibitor

PI3K

phosphatidylinositol 3-kinase

SB203580

p38 inhibitor

SRF

serum response factor

TLRs

Toll-like receptors

TNF-α

tumor necrosis factor-α

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Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  1. 1.Department of ImmunologyTuberculosis Research CentreChennaiIndia

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