Mycobacterium bovis BCG induces CXC chemokine ligand 8 secretion via the MEK-dependent signal pathway in human epithelial cells

Current knowledge of the cellular signaling by Mycobacterium bovis bacillus Calmette-Guerin (BCG) in epithelial cells is still limited. In this study, we provide evidence that the signaling events induced by M. bovis BCG in these cells included phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). Our data also demonstrate that M. bovis BCG-induced CXC chemokine ligand (CXCL)8 release in epithelial cells was reduced by a mitogen-activated protein/ERK kinase (MEK) inhibitor (PD98059), but not by a p38 MAPK (SB203580) inhibitor. In addition, we found that a second and more potent MEK inhibitor (U0126) significantly blocked CXCL8 release in epithelial cells by M. bovis BCG. Evaluation of CXCL8 RNA messages by reverse transcription-polymerase chain reaction (RT-PCR) revealed that the inhibitory effect of PD98059 and U0126 was associated with a reduction in this parameter. Moreover, the induction of CXCL8 secretion in epithelial cells by M. bovis BCG occurs at the transcription level. Collectively, the findings reported in the present study suggest that MEK signaling is essential for the induction of CXCL8 in epithelial cells in response to M. bovis BCG.