TY - JOUR
T1 - Role of reactive oxygen species (ROS) in Mycobacterium bovis bacillus Calmette Guérin-mediated up-regulation of the human cathelicidin LL-37 in A549 cells
AU - Méndez-Samperio, Patricia
AU - Pérez, Aline
AU - Torres, Laura
N1 - Funding Information:
This work was supported in part by grant 20090174 from the Secretaría de Investigación y Posgrado (SIP) del IPN. PMS is a research of COFAA, EDI, and SNI. The authors have no financial conflicts of interest.
PY - 2009/11
Y1 - 2009/11
N2 - The human cathelicidin LL-37 is one of the major antimicrobial peptides of the non-specific innate immune system in Mycobacterium tuberculosis infection. Its expression has been reported in epithelial cells infected with mycobacteria. However, the underlying molecular mechanisms by which Mycobacterium bovis bacillus Calmette-Guérin (BCG) triggers gene transcription of cathelicidin have not been elucidated. The objective of this study was to investigate the role of reactive oxygen species (ROS) in the M. bovis BCG-mediated up-regulation of the antimicrobial peptide cathelicidin LL-37 in human epithelial cells. Infection of A549 cells with M. bovis BCG led to a rapid ROS production. Importantly, blockade of ROS by preincubation of cells with the general ROS scavenger N-acetyl-l-cysteine (NAC) or the NADPH oxidase inhibitor DPI significantly reduced M. bovis BCG-induced up-regulation of cathelicidin LL-37 mRNA expression as determined by semi-quantitative RT-PCR or real-time PCR. In contrast, the xanthine oxidase inhibitor allopurinol did not affect M. bovis BCG-mediated up-regulation of cathelicidin LL-37 mRNA. Moreover, M. bovis BCG-mediated cathelicidin LL-37 mRNA expression was significantly blocked by the effect of the mitochondrial electron transfer chain subunit I inhibitor rotenone and H2O2 scavenging enzyme catalase. In addition, M. bovis BCG-induced cathelicidin LL-37 protein secretion was inhibited by the addition of NAC, DPI, and the selective inhibitor of NADPH oxidase apocynin. Our results collectively indicate that M. bovis BCG-mediated up-regulation of cathelicidin is influenced by NADPH/ROS signaling pathways. In conclusion, these findings demonstrate a novel regulatory mechanism for the expression of cathelicidin LL-37 in human epithelial cells stimulated with M. bovis BCG.
AB - The human cathelicidin LL-37 is one of the major antimicrobial peptides of the non-specific innate immune system in Mycobacterium tuberculosis infection. Its expression has been reported in epithelial cells infected with mycobacteria. However, the underlying molecular mechanisms by which Mycobacterium bovis bacillus Calmette-Guérin (BCG) triggers gene transcription of cathelicidin have not been elucidated. The objective of this study was to investigate the role of reactive oxygen species (ROS) in the M. bovis BCG-mediated up-regulation of the antimicrobial peptide cathelicidin LL-37 in human epithelial cells. Infection of A549 cells with M. bovis BCG led to a rapid ROS production. Importantly, blockade of ROS by preincubation of cells with the general ROS scavenger N-acetyl-l-cysteine (NAC) or the NADPH oxidase inhibitor DPI significantly reduced M. bovis BCG-induced up-regulation of cathelicidin LL-37 mRNA expression as determined by semi-quantitative RT-PCR or real-time PCR. In contrast, the xanthine oxidase inhibitor allopurinol did not affect M. bovis BCG-mediated up-regulation of cathelicidin LL-37 mRNA. Moreover, M. bovis BCG-mediated cathelicidin LL-37 mRNA expression was significantly blocked by the effect of the mitochondrial electron transfer chain subunit I inhibitor rotenone and H2O2 scavenging enzyme catalase. In addition, M. bovis BCG-induced cathelicidin LL-37 protein secretion was inhibited by the addition of NAC, DPI, and the selective inhibitor of NADPH oxidase apocynin. Our results collectively indicate that M. bovis BCG-mediated up-regulation of cathelicidin is influenced by NADPH/ROS signaling pathways. In conclusion, these findings demonstrate a novel regulatory mechanism for the expression of cathelicidin LL-37 in human epithelial cells stimulated with M. bovis BCG.
KW - Cathelicidin
KW - LL-37
KW - Mycobacteria
KW - Mycobacterium bovis BCG
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=70350129708&partnerID=8YFLogxK
U2 - 10.1016/j.micpath.2009.08.006
DO - 10.1016/j.micpath.2009.08.006
M3 - Artículo
C2 - 19729059
SN - 0882-4010
VL - 47
SP - 252
EP - 257
JO - Microbial Pathogenesis
JF - Microbial Pathogenesis
IS - 5
ER -