TY - JOUR
T1 - Regulation of human β-defensin-2 by Mycobacterium bovis bacillus Calmette-Guérin (BCG)
T2 - Involvement of PKC, JNK, and PI3K in human lung epithelial cell line (A549)
AU - Méndez-Samperio, Patricia
AU - Miranda, Elena
AU - Trejo, Artemisa
N1 - Funding Information:
This work was supported in part by grant no. 20080419 from the Coordinación General de Posgrado e Investigación de el IPN (CGPI). P.M.S. is a COFAA, EDI, and SNI fellow.
PY - 2008/10
Y1 - 2008/10
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.
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.
KW - Human β-defensin 2
KW - JNK
KW - Mycobacterium bovis BCG
KW - PI3K
KW - PKC
UR - http://www.scopus.com/inward/record.url?scp=52049084575&partnerID=8YFLogxK
U2 - 10.1016/j.peptides.2008.05.019
DO - 10.1016/j.peptides.2008.05.019
M3 - Artículo
SN - 0196-9781
VL - 29
SP - 1657
EP - 1663
JO - Peptides
JF - Peptides
IS - 10
ER -