Mycobacterium bovis Bacillus Calmette-Guérin (BCG) stimulates human beta-defensin-2 gene transcription in human epithelial cells.
Antimicrobial peptides produced by epithelial cells represent essential elements of innate immunity. Human beta-defensin-2 (hbetaD-2) is a major inducible antimicrobial peptide which plays an important role in host defense. The goal of this study was to determine the effect of Mycobacterium bovis bacillus Calmette-Guérin (BCG) on hbetaD-2 gene expression in epithelial cells, and to characterize further the signaling pathways involved in hbetaD-2 induction in response to M. bovis BCG. Using reverse transcription-polymerase chain reaction (RT-PCR), hbetaD-2 mRNA expression was detected in pulmonary epithelial cells infected with M. bovis BCG. Furthermore, we found that M. bovis BCG-induced hbetaD-2 mRNA expression was sustained by endogenous TNF-alpha in A549 cells. Of note, hbetaD-2 induction by M. bovis BCG was not blocked by pretreatment with anti-IL6 antibody. Moreover, hbetaD-2 mRNA expression was regulated at a transcriptional level, since hbetaD-2 induction by M. bovis BCG was blocked by two inhibitors of NF-kappaB. Taken together, these results suggest that M. bovis BCG infection of human epithelial cells induces hbetaD-2 mRNA expression which is up-regulated by TNF-alpha produced from M. bovis BCG-infected cells, and is modulated by NF-kappaB. Studies of hbetaD-2 mRNA regulation in epithelial cells infected with M. bovis BCG provide insight into how its expression may be enhanced to control Mycobacterium tuberculosis infection.
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
Miranda
Elena
E
Trejo
Artemisa
A
D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D009163:Mycobacterium bovis / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D023083:beta-Defensins / Q000235:genetics*
C106641:DEFB4A protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins