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.