Inhibition of TNF-alpha-induced cyclooxygenase-2 expression by Mycobacterium bovis BCG in human alveolar epithelial A549 cells.
Cyclooxygenase-2 (COX-2) is implicated in pathophysiological processes associated with the initiation or maintenance of host inflammatory responses to infection. Our results demonstrates that Mycobacterium bovis BCG (M. bovis BCG) downregulates tumour necrosis factor-alpha (TNF-alpha)-induced COX-2 gene expression in alveolar epithelial cells by inhibiting the phosphorylations of Raf-1 and p38 kinases. Further, M. bovis BCG-mediated inhibition of COX-2 or p38 mitogen-activated protein kinase could be reversed by Calyculin A, a selective inhibitor of Ser/Thr phosphatases. Moreover, M. bovis BCG inhibited the TNF-alpha-triggered NF-kappaB activation following IkappaB degradation. Taken together, these results suggest that the attenuation of COX-2 expression by vaccine strain, M. bovis BCG, represents a novel strategy to maintain robust host proinflammatory responses to subsequent challenges with virulent tuberculosis bacilli.
Bansal
K
K
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka, India.
Narayana
Y
Y
Balaji
K N
KN
D001500:BCG Vaccine; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008387:Marine Toxins; D009163:Mycobacterium bovis / Q000472:pathogenicity*; D016328:NF-kappa B / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000201:enzymology* / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D001500:BCG Vaccine; D020672:I-kappa B Proteins; D008387:Marine Toxins; D016328:NF-kappa B; D010080:Oxazoles; D014409:Tumor Necrosis Factor-alpha; C059041:calyculin A; D051546:Cyclooxygenase 2; D019908:Proto-Oncogene Proteins c-raf; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases