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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Mitogen activated protein kinase(p38) pathway is an important component of the anti-inflammatory response in Mycobacterium avium subsp. paratuberculosis-infected bovine monocytes.

We investigated the role of cell signaling through the mitogen-activated protein kinase-p38 (MAPK(p38)) pathway on the antimicrobial functions and cytokine expression by bovine monocytes after ingestion of Mycobacterium avium subsp. paratuberculosis. We evaluated the dynamic secretion of interleukin (IL)-10, IL-12 and tumor necrosis factor-alpha (TNF-alpha) as well as phagosome acidification and organism killing at several time points after in vitro infection of bovine monocytes with M. avium subsp. paratuberculosis. Monocytes treated with M. avium subsp. paratuberculosis had a significant increase in IL-10 expression at 2, 4, and 6h post-infection and an increase expression of TNF-alpha at 2, 4, 6, and 24h post-infection. In contrast, IL-12 expression did not increase at any time point post-infection. Moreover, MAPK(p38) was rapidly phosphorylated at 10 and 60min after M. avium subsp. paratuberculosis ingestion. Chemical inhibition of the MAPK(p38) signaling pathway (SB203580) resulted in decreased expression of IL-10 and increased expression of IL-12 at 6h post-infection. Chemically blocking the MAPK(p38) pathway also increased acidification of phagosomes as well as increasing the capacity of macrophages to kill organisms. Taken together, these results indicated that selective activation of MAPK(p38) may be a major mechanism exploited by M. avium subsp. paratuberculosis to circumvent the antimycobacterial effects of mononuclear phagocytes.[1]


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