Mycobacterium bovis-mediated induction of human beta-defensin-2 in epithelial cells is controlled by intracellular calcium and p38MAPK.
Induction of human beta defensin-2 (HBD-2) by mycobacteria has been reported. However, the molecular mechanism(s) by which mycobacteria up-regulates HBD-2 gene expression in epithelial cells remains poorly understood. In this work, we provide evidence that the induction of HBD-2 mRNA in response to Mycobacterium bovis bacillus Calmette-Guerin (BCG) was inhibited in a dose-dependent manner by pretreatment with a cell-permeable BAPTA-AM, which chelates intracellular calcium. Our data also demonstrate that HBD-2 mRNA induction by M. bovis in A549 lung epithelial cells requires activation of calmodulin. Interestingly, HBD-2 mRNA expression in response to M. bovis BCG was attenuated by pretreatment with SB203580 (an inhibitor of p38 mitogen-activated protein kinase [MAPK]), but not by an inhibitor of extracellular signal-regulated kinase (ERK): PD98059. Furthermore, we found that a second p38 MAPK inhibitor (SB202190) significantly blocked M. bovis BCG-mediated HBD-2 induction in A549 lung epithelial cells. Together, these data suggest that M. bovis BCG induces HBD-2 mRNA expression in A549 lung epithelial cells at least in part mediated through intracellular calcium flux as well as activation of signaling protein of p38MAPK, but not ERK.
Méndez-Samperio
Patricia
P
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Carpio y Plan de Ayala, México D.F. 11340, Mexico. pmendezs@bios.encb.ipn.mx
Alba
Laura
L
Trejo
Artemisa
A
D000890:Anti-Infective Agents / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology*; D005786:Gene Expression Regulation; D006801:Humans; D009163:Mycobacterium bovis / Q000472:pathogenicity*; D015398:Signal Transduction; D015854:Up-Regulation; D023083:beta-Defensins / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000494:pharmacology*
D000890:Anti-Infective Agents; D023083:beta-Defensins; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium