Cover American Journal of Veterinary Research
American Journal of Veterinary Research
ISSN:
0002-9645
Publication Date:
01 Oct 2006
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Editorial Type:
Infectious Disease

Regulation by Jun N-terminal kinase/stress activated protein kinase of cytokine expression in Mycobacterium avium subsp paratuberculosis–infected bovine monocytes

Cleverson D. Souza DVM, MS1, Oral A. Evanson BS2, and Douglas J. Weiss DVM, PhD3
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  • 1 Department of Veterinary and Biomedical Science, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, 55018.
  • | 2 Department of Veterinary and Biomedical Science, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, 55018.
  • | 3 Department of Veterinary and Biomedical Science, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, 55018.
DOI:
https://doi.org/10.2460/ajvr.67.10.1760
Volume/Issue:
Volume 67: Issue 10
Online Publication Date:
01 Oct 2006
Restricted access
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Abstract

Objective—To evaluate activation of Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway in bovine monocytes after incubation with Mycobacterium avium subsp paratuberculosis (Mptb) organisms.

Sample Population—Bovine monocytes obtained from 4 healthy adult Holstein dairy cows.

Procedures—Bovine monocytes were incubated with Mptb organisms with or without a specific inhibitor of the JNK/SAPK pathway (SP600125) for 2, 6, 24, or 72 hours. Expression of interleukin (IL)-1β, IL-10, IL-12, IL-18; transforming growth factor-β (TGF-β); and tumor necrosis factor-α (TNF-α) and the capacity of Mptb-infected monocytes to acidify phagosomes and kill Mptb organisms were evaluated. Phosphorylation status of JNK/SAPK was evaluated at 10, 30, and 60 minutes after Mptb incubation.

Results—Compared with uninfected control monocytes, Mptb-infected monocytes had increased expression of IL-10 at 2 and 6 hours after incubation and had increased expression of TNF-α, IL-1β, IL-18, and TGF-β at 2, 4, and 6 hours. Additionally, Mptb-infected monocytes had increased expression of IL-12 at 6 and 24 hours. Addition of SP600125 (specific chemical inhibitor of JNK/SAPK) resulted in a decrease in TNF-α expression at 2, 6, and 24 hours, compared with untreated Mptb-infected cells. Addition of SP600125 resulted in a decrease in TGF-β expression at 24 hours and an increase in IL-18 expression at 6 hours. Addition of SP600125 failed to alter phagosome acidification but did enhance the capacity of monocytes to kill Mptb organisms.

Conclusions and Clinical Relevance—Activation of JNK/SAPK may be an important mechanism used by Mptb to regulate cytokine expression in bovine monocytes for survival and to alter inflammatory and immune responses.

Abstract

Objective—To evaluate activation of Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway in bovine monocytes after incubation with Mycobacterium avium subsp paratuberculosis (Mptb) organisms.

Sample Population—Bovine monocytes obtained from 4 healthy adult Holstein dairy cows.

Procedures—Bovine monocytes were incubated with Mptb organisms with or without a specific inhibitor of the JNK/SAPK pathway (SP600125) for 2, 6, 24, or 72 hours. Expression of interleukin (IL)-1β, IL-10, IL-12, IL-18; transforming growth factor-β (TGF-β); and tumor necrosis factor-α (TNF-α) and the capacity of Mptb-infected monocytes to acidify phagosomes and kill Mptb organisms were evaluated. Phosphorylation status of JNK/SAPK was evaluated at 10, 30, and 60 minutes after Mptb incubation.

Results—Compared with uninfected control monocytes, Mptb-infected monocytes had increased expression of IL-10 at 2 and 6 hours after incubation and had increased expression of TNF-α, IL-1β, IL-18, and TGF-β at 2, 4, and 6 hours. Additionally, Mptb-infected monocytes had increased expression of IL-12 at 6 and 24 hours. Addition of SP600125 (specific chemical inhibitor of JNK/SAPK) resulted in a decrease in TNF-α expression at 2, 6, and 24 hours, compared with untreated Mptb-infected cells. Addition of SP600125 resulted in a decrease in TGF-β expression at 24 hours and an increase in IL-18 expression at 6 hours. Addition of SP600125 failed to alter phagosome acidification but did enhance the capacity of monocytes to kill Mptb organisms.

Conclusions and Clinical Relevance—Activation of JNK/SAPK may be an important mechanism used by Mptb to regulate cytokine expression in bovine monocytes for survival and to alter inflammatory and immune responses.

Contributor Notes

Supported in part by a grant from the University of Minnesota, Academic Health Center and USDA-NRI 2005-010447. Dr. Souza is a Research Fellow of the Coordenacao de Aperfeicoamento de Pessoal de Nível Superior, Brazil.

Address correspondence to Dr. Souza.