Role of the MAPK super(ERK) pathway in regulation of cytokine expression by Mycobacterium avium subsp paratuberculosis-exposed bovine monocytes

Objective--To evaluate the role of the mitogen-activated protein kinase extracellular signal-regulated kinase (MAPK super(ERK)) pathway in the interaction between Mycobacterium avium subsp paratuberculosis (MAP) organisms and bovine monocytes. Sample Population--Monocytes obtained from healthy adult Holstein dairy cows that were not infected with MAP organisms. Procedures--Monocytes and MAP organisms were incubated together with or without a specific inhibitor of the MAPK super(ERK) pathway (PD98059), and the capacity of monocytes to express tumor necrosis factor alpha (TNF)-a and interleukin (IL)-10 and -12, produce nitric oxide, acidify phagosomes, kill MAP organisms, and undergo apoptosis was evaluated. Results--The MAPK super(ERK) pathway was activated within 10 minutes after addition of MAP organisms to monocytes. Addition of PD98059 to monocyte-MAP mixtures decreased monocyte TNF-a and IL-12 mRNA expression but had no effect on IL-10 mRNA expression. Treatment with PD98059 failed to induce significant alterations in phagosome acidification, organism killing, nitric oxide production, or apoptosis of MAP-exposed monocytes. Conclusions and Clinical Relevance--Results indicated that the MAPK super(ERK) pathway was activated during the interaction of MAP organisms with monocytes, which initiated TNF-a and IL-12 mRNA expression but failed to initiate antimicrobial activity. The MAPK super(ERK) pathway may be involved in initiating proinflammatory and proimmune responses in MAP infection in cattle.