Mycobacterium bovis Bacillus Calmette-Guérin (BCG) stimulates IL-10 production via the PI3K/Akt and p38 MAPK pathways in human lung epithelial cells.
Infection of human cells with mycobacteria has been shown to result in the production of anti-inflammatory cytokines. However, the signaling pathways that regulate the Mycobacterium bovis BCG-induced interleukin (IL)-10 production are currently unknown. In the present study, we investigated the involvement of phosphatidylinoditol 3-kinase (PI3K)/Akt and the p38 MAPK signaling pathways in the secretion of IL-10 in human lung epithelial cells (A549) after infection with M. bovis BCG. Treatment of A549 cells with LY 294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) and wortmannin, two PI3K inhibitors, inhibited M. bovis BCG-induced IL-10 production. Stimulation of cells with M. bovis BCG caused an increase in Akt phosphorylation in a time-dependent manner, which was inhibited by wortmannin. In addition, treatment of A549 cells with an Akt inhibitor significantly blocked M. bovis BCG-induced IL-10 production. Moreover, the p38 inhibitor SB203580 significantly decreased IL-10 production in a dose-dependent manner, whereas M. bovis BCG-induced IL-10 secretion was completely unaffected by the MEK inhibitor PD98059. Finally, the inhibition of PI3K did not significantly affect p38 MAPK activation in M. bovis BCG-infected cells, indicating that PI3K activity is not required for the M. bovis BCG-induced phosphorylation of p38 MAPK. Collectively, these data suggest that the PI3K/Akt and p38 MAPK signaling pathways play an important role in the regulation of M. bovis BCG-induced IL-10 secretion in A549 cells.
Méndez-Samperio
Patricia
P
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Carpio y Plan de Ayala, México DF 11340, Mexico. pmendezs@bios.encb.ipn.mx
Trejo
Artemisa
A
Pérez
Aline
A
D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D008168:Lung / Q000166:cytology; D009163:Mycobacterium bovis / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases