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

Natarajan, P L and Narayanan, Sujatha (2011) Mitogen-activated protein kinases mediate the production of B-cell lymphoma 2 protein by Mycobacterium tuberculosis in monocytes. Biochemistry, 76 (8). pp. 938-950. ISSN Print: 0006-2960 | Electronic: 1520-4995

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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.

Affiliation:	ICMR-National Institute for Research in Tuberculosis
Item Type:	Article
Uncontrolled Keywords:	M. tuberculosis, ERK, p38 MAPK, Bcl�2 production, NF-κB
Subjects:	Tuberculosis > Laboratory Research > Immunological
Divisions:	Basic Science Research > Immunology
Depositing User:	Dr. Rathinasabapati R
Date Deposited:	20 Jun 2022 10:41
Last Modified:	20 Jun 2022 10:41
URI:	http://eprints.nirt.res.in/id/eprint/1106

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