Role of the MAPK(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(ERK)) pathway in the interaction between Mycobacterium avium subsp paratuberculosis (MAP) organisms and bovine monocytes.


METHODS
Monocytes obtained from healthy adult Holstein dairy cows that were not infected with MAP organisms.


METHODS
Monocytes and MAP organisms were incubated together with or without a specific inhibitor of the MAPK(ERK) pathway (PD98059), and the capacity of monocytes to express tumor necrosis factor alpha (TNF)-alpha and interleukin (IL)-10 and -12, produce nitric oxide, acidify phagosomes, kill MAP organisms, and undergo apoptosis was evaluated.


RESULTS
The MAPK(ERK) pathway was activated within 10 minutes after addition of MAP organisms to monocytes. Addition of PD98059 to monocyte-MAP mixtures decreased monocyte TNF-alpha 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
Results indicated that the MAPK(ERK) pathway was activated during the interaction of MAP organisms with monocytes, which initiated TNF-alpha and IL-12 mRNA expression but failed to initiate antimicrobial activity. The MAPK(ERK) pathway may be involved in initiating proinflammatory and proimmune responses in MAP infection in cattle.
Souza
Cleverson D
CD
Department of Veterinary and Biomedical Science, University of Minnesota, Saint Paul, MN 55108, USA.
Evanson
Oral A
OA
Weiss
Douglas J
DJ
D000818:Animals; D002417:Cattle / Q000097:blood*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*; D016927:Mycobacterium avium subsp. paratuberculosis / Q000502:physiology*; D010587:Phagocytosis
D016207:Cytokines; D004791:Enzyme Inhibitors; D005419:Flavonoids; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one