Regulation of human β-defensin-2 by Mycobacterium bovis bacillus Calmette-Guérin (BCG): Involvement of PKC, JNK, and PI3K in human lung epithelial cell line (A549)

Patricia Méndez-Samperio, Elena Miranda, Artemisa Trejo

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15 Citations (Scopus)

Abstract

Human β-defensin (HBD)-2 is an inducible antimicrobial peptide that plays an important role in innate immunity. Induction of this peptide by mycobacteria in epithelial cells has been reported. However, the mechanism(s) by which Mycobacterium bovis bacillus Calmette-Guérin (BCG) triggers gene transcription of HBD-2 remains poorly understood. In the present work we found that treatment of human epithelial cells with Ro32-0432 or Gö6976, two selective inhibitors of protein kinase C (PKC), significantly reduced the effect of M. bovis BCG on induced HBD-2 mRNA expression (65 and 80% inhibition by 10 μM Ro32-0432, and 1 μM Gö6976 as assessed by real-time PCR, respectively). Moreover, there was increased activation of c-Jun N-terminal kinase (JNK) and phosphatidylinositol-3-kinase (PI3K)/Akt in A549 cells infected with M. bovis BCG, and this JNK and PI3K activation was mediated through PKC. Finally, we found that M. bovis BCG-induced HBD-2 mRNA gene expression in A549 cells was dependent on JNK, and PI3K determined by real-time PCR analysis, which was attenuated by inhibitors of JNK (SP600125 and AG126), and PI3K (wortmannin and Ly294002). These studies are the first to show that M. bovis BCG-induced HBD-2 mRNA expression in A549 cells is regulated at least in part through activation of signaling proteins of PKC, JNK and PI3K. © 2008 Elsevier Inc. All rights reserved.
Original languageAmerican English
Pages (from-to)1657-1663
Number of pages1490
JournalPeptides
DOIs
StatePublished - 1 Oct 2008

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Phosphatidylinositol 3-Kinase
Defensins
Bacillus
Bacilli
Mycobacterium bovis
cultured cells
lungs
Protein Kinase C
Phosphotransferases
Epithelial Cells
proteins
Proteins
Cell Line
Lung
Chemical activation
activation
inhibitors
Messenger RNA
Peptides
peptides

Cite this

@article{86db09b8a9c24d89a5a31a7236a5cb1b,
title = "Regulation of human β-defensin-2 by Mycobacterium bovis bacillus Calmette-Gu{\'e}rin (BCG): Involvement of PKC, JNK, and PI3K in human lung epithelial cell line (A549)",
abstract = "Human β-defensin (HBD)-2 is an inducible antimicrobial peptide that plays an important role in innate immunity. Induction of this peptide by mycobacteria in epithelial cells has been reported. However, the mechanism(s) by which Mycobacterium bovis bacillus Calmette-Gu{\'e}rin (BCG) triggers gene transcription of HBD-2 remains poorly understood. In the present work we found that treatment of human epithelial cells with Ro32-0432 or G{\"o}6976, two selective inhibitors of protein kinase C (PKC), significantly reduced the effect of M. bovis BCG on induced HBD-2 mRNA expression (65 and 80{\%} inhibition by 10 μM Ro32-0432, and 1 μM G{\"o}6976 as assessed by real-time PCR, respectively). Moreover, there was increased activation of c-Jun N-terminal kinase (JNK) and phosphatidylinositol-3-kinase (PI3K)/Akt in A549 cells infected with M. bovis BCG, and this JNK and PI3K activation was mediated through PKC. Finally, we found that M. bovis BCG-induced HBD-2 mRNA gene expression in A549 cells was dependent on JNK, and PI3K determined by real-time PCR analysis, which was attenuated by inhibitors of JNK (SP600125 and AG126), and PI3K (wortmannin and Ly294002). These studies are the first to show that M. bovis BCG-induced HBD-2 mRNA expression in A549 cells is regulated at least in part through activation of signaling proteins of PKC, JNK and PI3K. {\circledC} 2008 Elsevier Inc. All rights reserved.",
author = "Patricia M{\'e}ndez-Samperio and Elena Miranda and Artemisa Trejo",
year = "2008",
month = "10",
day = "1",
doi = "10.1016/j.peptides.2008.05.019",
language = "American English",
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Regulation of human β-defensin-2 by Mycobacterium bovis bacillus Calmette-Guérin (BCG): Involvement of PKC, JNK, and PI3K in human lung epithelial cell line (A549). / Méndez-Samperio, Patricia; Miranda, Elena; Trejo, Artemisa.

In: Peptides, 01.10.2008, p. 1657-1663.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Regulation of human β-defensin-2 by Mycobacterium bovis bacillus Calmette-Guérin (BCG): Involvement of PKC, JNK, and PI3K in human lung epithelial cell line (A549)

AU - Méndez-Samperio, Patricia

AU - Miranda, Elena

AU - Trejo, Artemisa

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Human β-defensin (HBD)-2 is an inducible antimicrobial peptide that plays an important role in innate immunity. Induction of this peptide by mycobacteria in epithelial cells has been reported. However, the mechanism(s) by which Mycobacterium bovis bacillus Calmette-Guérin (BCG) triggers gene transcription of HBD-2 remains poorly understood. In the present work we found that treatment of human epithelial cells with Ro32-0432 or Gö6976, two selective inhibitors of protein kinase C (PKC), significantly reduced the effect of M. bovis BCG on induced HBD-2 mRNA expression (65 and 80% inhibition by 10 μM Ro32-0432, and 1 μM Gö6976 as assessed by real-time PCR, respectively). Moreover, there was increased activation of c-Jun N-terminal kinase (JNK) and phosphatidylinositol-3-kinase (PI3K)/Akt in A549 cells infected with M. bovis BCG, and this JNK and PI3K activation was mediated through PKC. Finally, we found that M. bovis BCG-induced HBD-2 mRNA gene expression in A549 cells was dependent on JNK, and PI3K determined by real-time PCR analysis, which was attenuated by inhibitors of JNK (SP600125 and AG126), and PI3K (wortmannin and Ly294002). These studies are the first to show that M. bovis BCG-induced HBD-2 mRNA expression in A549 cells is regulated at least in part through activation of signaling proteins of PKC, JNK and PI3K. © 2008 Elsevier Inc. All rights reserved.

AB - Human β-defensin (HBD)-2 is an inducible antimicrobial peptide that plays an important role in innate immunity. Induction of this peptide by mycobacteria in epithelial cells has been reported. However, the mechanism(s) by which Mycobacterium bovis bacillus Calmette-Guérin (BCG) triggers gene transcription of HBD-2 remains poorly understood. In the present work we found that treatment of human epithelial cells with Ro32-0432 or Gö6976, two selective inhibitors of protein kinase C (PKC), significantly reduced the effect of M. bovis BCG on induced HBD-2 mRNA expression (65 and 80% inhibition by 10 μM Ro32-0432, and 1 μM Gö6976 as assessed by real-time PCR, respectively). Moreover, there was increased activation of c-Jun N-terminal kinase (JNK) and phosphatidylinositol-3-kinase (PI3K)/Akt in A549 cells infected with M. bovis BCG, and this JNK and PI3K activation was mediated through PKC. Finally, we found that M. bovis BCG-induced HBD-2 mRNA gene expression in A549 cells was dependent on JNK, and PI3K determined by real-time PCR analysis, which was attenuated by inhibitors of JNK (SP600125 and AG126), and PI3K (wortmannin and Ly294002). These studies are the first to show that M. bovis BCG-induced HBD-2 mRNA expression in A549 cells is regulated at least in part through activation of signaling proteins of PKC, JNK and PI3K. © 2008 Elsevier Inc. All rights reserved.

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