Reactive Oxygen Species-activated p38/ERK 1/2 MAPK Signaling Pathway in the Mycobacterium bovis Bacillus Calmette Guérin (BCG)-induced CCL2 Secretion in Human Monocytic Cell Line THP-1

Patricia Méndez-Samperio, Aline Pérez, Laura Alba

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Abstract

Background and Aims: CCL2 plays an important role in mycobacterial infection by inducing leukocyte recruitment and activation. Here we assess the role of reactive oxygen species (ROS) in the secretion of the CCL2 and the activation of mitogen-activated protein kinases (MAPKs) by human monocytic cells infected with Mycobacterium bovis bacillus Calmette Guérin (BCG). Methods: CCL2 mRNA and protein expression were measured by reverse transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and ELISA. Kinase phosphorylation was determined by immunoblotting. Results: Treatment of human monocytic cells with M. bovis BCG activated rapid superoxide generation. mRNA expression of CCL2 was increased in M. bovis BCG-infected monocytic cells, and this increase was abrogated by administration of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenyleneiodonium (DPI). Importantly, M. bovis BCG-induced CCL2 protein secretion was also inhibited by the NADPH oxidase inhibitor DPI, the selective inhibitor of NADPH oxidase apocynin, the mitochondrial electron transfer chain subunit I inhibitor rotenone and H2O2 scavenging enzyme catalase, indicating that the inhibition is through the NADPH/ROS pathway. Analysis of downstream signals showed that inhibition of NADPH oxidase inhibited M. bovis BCG-induced phosphorylation of MAPK (extracellular signal-regulated kinase (ERK) 1/2 and p38). Conclusions: These results strongly suggest that NADPH oxidase-derived ROS-mediated activation of p38 and ERK 1/2 is essential for the M. bovis BCG-induced CCL2 production. © 2010 IMSS.
Original languageAmerican English
Pages (from-to)579-585
Number of pages520
JournalArchives of Medical Research
DOIs
StatePublished - 1 Nov 2010

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nicotinamide
secretions
Mitogen-Activated Protein Kinase 3
Bacillus
Mitogen-Activated Protein Kinase 1
adenines
Bacilli
Mycobacterium bovis
Mitogen-Activated Protein Kinases
NADP
cultured cells
oxidase
Reactive Oxygen Species
phosphates
Phosphates
Cells
Oxidoreductases
proteins
Proteins
Cell Line

Cite this

@article{03a41b28908c43d399460711294af72b,
title = "Reactive Oxygen Species-activated p38/ERK 1/2 MAPK Signaling Pathway in the Mycobacterium bovis Bacillus Calmette Gu{\'e}rin (BCG)-induced CCL2 Secretion in Human Monocytic Cell Line THP-1",
abstract = "Background and Aims: CCL2 plays an important role in mycobacterial infection by inducing leukocyte recruitment and activation. Here we assess the role of reactive oxygen species (ROS) in the secretion of the CCL2 and the activation of mitogen-activated protein kinases (MAPKs) by human monocytic cells infected with Mycobacterium bovis bacillus Calmette Gu{\'e}rin (BCG). Methods: CCL2 mRNA and protein expression were measured by reverse transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and ELISA. Kinase phosphorylation was determined by immunoblotting. Results: Treatment of human monocytic cells with M. bovis BCG activated rapid superoxide generation. mRNA expression of CCL2 was increased in M. bovis BCG-infected monocytic cells, and this increase was abrogated by administration of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenyleneiodonium (DPI). Importantly, M. bovis BCG-induced CCL2 protein secretion was also inhibited by the NADPH oxidase inhibitor DPI, the selective inhibitor of NADPH oxidase apocynin, the mitochondrial electron transfer chain subunit I inhibitor rotenone and H2O2 scavenging enzyme catalase, indicating that the inhibition is through the NADPH/ROS pathway. Analysis of downstream signals showed that inhibition of NADPH oxidase inhibited M. bovis BCG-induced phosphorylation of MAPK (extracellular signal-regulated kinase (ERK) 1/2 and p38). Conclusions: These results strongly suggest that NADPH oxidase-derived ROS-mediated activation of p38 and ERK 1/2 is essential for the M. bovis BCG-induced CCL2 production. {\circledC} 2010 IMSS.",
author = "Patricia M{\'e}ndez-Samperio and Aline P{\'e}rez and Laura Alba",
year = "2010",
month = "11",
day = "1",
doi = "10.1016/j.arcmed.2010.10.009",
language = "American English",
pages = "579--585",
journal = "Archives of Medical Research",
issn = "0188-4409",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Reactive Oxygen Species-activated p38/ERK 1/2 MAPK Signaling Pathway in the Mycobacterium bovis Bacillus Calmette Guérin (BCG)-induced CCL2 Secretion in Human Monocytic Cell Line THP-1

AU - Méndez-Samperio, Patricia

AU - Pérez, Aline

AU - Alba, Laura

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Background and Aims: CCL2 plays an important role in mycobacterial infection by inducing leukocyte recruitment and activation. Here we assess the role of reactive oxygen species (ROS) in the secretion of the CCL2 and the activation of mitogen-activated protein kinases (MAPKs) by human monocytic cells infected with Mycobacterium bovis bacillus Calmette Guérin (BCG). Methods: CCL2 mRNA and protein expression were measured by reverse transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and ELISA. Kinase phosphorylation was determined by immunoblotting. Results: Treatment of human monocytic cells with M. bovis BCG activated rapid superoxide generation. mRNA expression of CCL2 was increased in M. bovis BCG-infected monocytic cells, and this increase was abrogated by administration of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenyleneiodonium (DPI). Importantly, M. bovis BCG-induced CCL2 protein secretion was also inhibited by the NADPH oxidase inhibitor DPI, the selective inhibitor of NADPH oxidase apocynin, the mitochondrial electron transfer chain subunit I inhibitor rotenone and H2O2 scavenging enzyme catalase, indicating that the inhibition is through the NADPH/ROS pathway. Analysis of downstream signals showed that inhibition of NADPH oxidase inhibited M. bovis BCG-induced phosphorylation of MAPK (extracellular signal-regulated kinase (ERK) 1/2 and p38). Conclusions: These results strongly suggest that NADPH oxidase-derived ROS-mediated activation of p38 and ERK 1/2 is essential for the M. bovis BCG-induced CCL2 production. © 2010 IMSS.

AB - Background and Aims: CCL2 plays an important role in mycobacterial infection by inducing leukocyte recruitment and activation. Here we assess the role of reactive oxygen species (ROS) in the secretion of the CCL2 and the activation of mitogen-activated protein kinases (MAPKs) by human monocytic cells infected with Mycobacterium bovis bacillus Calmette Guérin (BCG). Methods: CCL2 mRNA and protein expression were measured by reverse transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and ELISA. Kinase phosphorylation was determined by immunoblotting. Results: Treatment of human monocytic cells with M. bovis BCG activated rapid superoxide generation. mRNA expression of CCL2 was increased in M. bovis BCG-infected monocytic cells, and this increase was abrogated by administration of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenyleneiodonium (DPI). Importantly, M. bovis BCG-induced CCL2 protein secretion was also inhibited by the NADPH oxidase inhibitor DPI, the selective inhibitor of NADPH oxidase apocynin, the mitochondrial electron transfer chain subunit I inhibitor rotenone and H2O2 scavenging enzyme catalase, indicating that the inhibition is through the NADPH/ROS pathway. Analysis of downstream signals showed that inhibition of NADPH oxidase inhibited M. bovis BCG-induced phosphorylation of MAPK (extracellular signal-regulated kinase (ERK) 1/2 and p38). Conclusions: These results strongly suggest that NADPH oxidase-derived ROS-mediated activation of p38 and ERK 1/2 is essential for the M. bovis BCG-induced CCL2 production. © 2010 IMSS.

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U2 - 10.1016/j.arcmed.2010.10.009

DO - 10.1016/j.arcmed.2010.10.009

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JF - Archives of Medical Research

SN - 0188-4409

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