Effects of nuclear factor-κB on regulation of cytokine expression and apoptosis in bovine monocytes exposed to Mycobacterium avium subsp paratuberculosis

Objective—To evaluate the role of the nuclear factor-κB (NF-κB) in the response of bovine monocytes to exposure to Mycobacterium avium subsp paratuberculosis (MAP). Sample Population—Monocytes from healthy adult Holstein cows that were known to be negative for MAP infection. Procedures—Monocytes were incubated with MAP organisms with or without a specific inhibitor of the NF-κB pathway (pyrrolidine dithiocarbamate), and activation of the NF-κB pathway was detected by use of an electrophorectic mobility shift assay. The capacities of monocytes to express tumor necrosis factor (TNF)-α, interleukin (IL)-10, and IL-12; to acidify phagosomes; to phagocytize and kill MAP organisms; and to undergo apoptosis were evaluated. Results—Addition of MAP organisms to monocytes activated the NF-κB pathway as indicated by increased NF-κB–DNA binding. Addition of pyrrolidine dithiocarbamate prevented nuclear translocation of NF-κB, decreased expression of TNF-α and IL-10, and increased IL-12 expression. Treatment of MAP-ex...