1887

Abstract

Src family kinases (SFKs) are non-receptor tyrosine kinases that have been implicated as regulators of the inflammatory response. In this study, the role of SFK activation in the inflammatory response of macrophages to encephalomyocarditis virus (EMCV) infection was examined. Virus infection of macrophages stimulates the expression of cyclooxygenase-2 (COX-2), interleukin (IL)-1 and inducible nitric oxide synthase (iNOS). Inhibition of SFK attenuates EMCV-induced COX-2 expression and prostaglandin E production, iNOS expression and subsequent nitric oxide production, and IL-1 expression. EMCV-induced COX-2 expression requires the activation of nuclear factor-B and the mitogen-activated protein kinase p38. Consistent with these previous findings, inhibition of SFKs attenuated the phosphorylation of p38 in response to EMCV infection, suggesting that SFKs may act upstream of p38. These findings provide evidence that SFK activation plays an active role in the regulation of inflammatory gene expression by virus-infected macrophages.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.022665-0
2010-09-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/9/2278.html?itemId=/content/journal/jgv/10.1099/vir.0.022665-0&mimeType=html&fmt=ahah

References

  1. Arend, W. P., Palmer, G. & Gabay, C.(2008). IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev 223, 20–38.[CrossRef] [Google Scholar]
  2. Arnush, M., Scarim, A. L., Heitmeier, M. R., Kelly, C. B. & Corbett, J. A.(1998). Potential role of resident islet macrophage activation in the initiation of autoimmune diabetes. J Immunol 160, 2684–2691. [Google Scholar]
  3. Bae, Y. S., Eun, H. M. & Yoon, J. W.(1989). Genomic differences between the diabetogenic and nondiabetogenic variants of encephalomyocarditis virus. Virology 170, 282–287.[CrossRef] [Google Scholar]
  4. Beckerman, K. P., Rogers, H. W., Corbett, J. A., Schreiber, R. D., McDaniel, M. L. & Unanue, E. R.(1993). Release of nitric oxide during the T cell-independent pathway of macrophage activation. Its role in resistance to Listeria monocytogenes. J Immunol 150, 888–895. [Google Scholar]
  5. Boulet, I., Ralph, S., Stanley, E., Lock, P., Dunn, A. R., Green, S. P. & Phillips, W. A.(1992). Lipopolysaccharide- and interferon-γ-induced expression of hck and lyn tyrosine kinases in murine bone marrow-derived macrophages. Oncogene 7, 703–710. [Google Scholar]
  6. Choi, K. S., Jun, H. S., Kim, H. N., Park, H. J., Eom, Y. W., Noh, H. L., Kwon, H., Kim, H. M. & Yoon, J. W.(2001). Role of Hck in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice. J Virol 75, 1949–1957.[CrossRef] [Google Scholar]
  7. English, B. K., Orlicek, S. L., Mei, Z. & Meals, E. A.(1997). Bacterial LPS and IFN-γ trigger the tyrosine phosphorylation of vav in macrophages: evidence for involvement of the hck tyrosine kinase. J Leukoc Biol 62, 859–864. [Google Scholar]
  8. Gitlin, L., Barchet, W., Gilfillan, S., Cella, M., Beutler, B., Flavell, R. A., Diamond, M. S. & Colonna, M.(2006). Essential role of mda-5 in type I IFN responses to polyriboinosinic : polyribocytidylic acid and encephalomyocarditis picornavirus. Proc Natl Acad Sci U S A 103, 8459–8464.[CrossRef] [Google Scholar]
  9. Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S. & Tannenbaum, S. R.(1982). Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126, 131–138.[CrossRef] [Google Scholar]
  10. Heitmeier, M. R., Scarim, A. L. & Corbett, J. A.(1998). Double-stranded RNA-induced inducible nitric-oxide synthase expression and interleukin-1 release by murine macrophages requires NF-κB activation. J Biol Chem 273, 15301–15307.[CrossRef] [Google Scholar]
  11. Huang, W. C., Chen, J. J., Inoue, H. & Chen, C. C.(2003). Tyrosine phosphorylation of I-κB kinase α/β by protein kinase C-dependent c-Src activation is involved in TNF-α-induced cyclooxygenase-2 expression. J Immunol 170, 4767–4775.[CrossRef] [Google Scholar]
  12. Iordanov, M. S., Paranjape, J. M., Zhou, A., Wong, J., Williams, B. R., Meurs, E. F., Silverman, R. H. & Magun, B. E.(2000). Activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase by double-stranded RNA and encephalomyocarditis virus: involvement of RNase L, protein kinase R, and alternative pathways. Mol Cell Biol 20, 617–627.[CrossRef] [Google Scholar]
  13. Johnsen, I. B., Nguyen, T. T., Ringdal, M., Tryggestad, A. M., Bakke, O., Lien, E., Espevik, T. & Anthonsen, M. W.(2006). Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling. EMBO J 25, 3335–3346.[CrossRef] [Google Scholar]
  14. Karupiah, G., Xie, Q. W., Buller, R. M., Nathan, C., Duarte, C. & MacMicking, J. D.(1993). Inhibition of viral replication by interferon-γ-induced nitric oxide synthase. Science 261, 1445–1448.[CrossRef] [Google Scholar]
  15. Leu, T. H., Charoenfuprasert, S., Yen, C. K., Fan, C. W. & Maa, M. C.(2006). Lipopolysaccharide-induced c-Src expression plays a role in nitric oxide and TNFα secretion in macrophages. Mol Immunol 43, 308–316.[CrossRef] [Google Scholar]
  16. Lowell, C. A.(2004). Src-family kinases: rheostats of immune cell signaling. Mol Immunol 41, 631–643.[CrossRef] [Google Scholar]
  17. Ma, Y. C., Huang, J., Ali, S., Lowry, W. & Huang, X. Y.(2000). Src tyrosine kinase is a novel direct effector of G proteins. Cell 102, 635–646.[CrossRef] [Google Scholar]
  18. Maggi, L. B., Jr, Moran, J. M., Scarim, A. L., Ford, D. A., Yoon, J. W., McHowat, J., Buller, R. M. & Corbett, J. A.(2002). Novel role for calcium-independent phospholipase A2 in the macrophage antiviral response of inducible nitric-oxide synthase expression. J Biol Chem 277, 38449–38455.[CrossRef] [Google Scholar]
  19. Maggi, L. B., Jr, Moran, J. M., Buller, R. M. & Corbett, J. A.(2003). ERK activation is required for double-stranded RNA- and virus-induced interleukin-1 expression by macrophages. J Biol Chem 278, 16683–16689.[CrossRef] [Google Scholar]
  20. McGarrigle, D. & Huang, X. Y.(2007). GPCRs signaling directly through Src-family kinases. Sci STKE 2007, pe35 [Google Scholar]
  21. Medzhitov, R.(2007). Recognition of microorganisms and activation of the immune response. Nature 449, 819–826.[CrossRef] [Google Scholar]
  22. Mocsai, A., Jakus, Z., Vantus, T., Berton, G., Lowell, C. A. & Ligeti, E.(2000). Kinase pathways in chemoattractant-induced degranulation of neutrophils: the role of p38 mitogen-activated protein kinase activated by Src family kinases. J Immunol 164, 4321–4331.[CrossRef] [Google Scholar]
  23. Moran, J. M., Moxley, M. A., Buller, R. M. & Corbett, J. A.(2005). Encephalomyocarditis virus induces PKR-independent mitogen-activated protein kinase activation in macrophages. J Virol 79, 10226–10236.[CrossRef] [Google Scholar]
  24. Okutani, D., Lodyga, M., Han, B. & Liu, M.(2006). Src protein tyrosine kinase family and acute inflammatory responses. Am J Physiol Lung Cell Mol Physiol 291, L129–L141.[CrossRef] [Google Scholar]
  25. Orlicek, S. L., Hanke, J. H. & English, B. K.(1999). The src family-selective tyrosine kinase inhibitor PP1 blocks LPS and IFN-γ-mediated TNF and iNOS production in murine macrophages. Shock 12, 350–354.[CrossRef] [Google Scholar]
  26. Parsons, S. J. & Parsons, J. T.(2004). Src family kinases, key regulators of signal transduction. Oncogene 23, 7906–7909.[CrossRef] [Google Scholar]
  27. Saura, M., Zaragoza, C., McMillan, A., Quick, R. A., Hohenadl, C., Lowenstein, J. M. & Lowenstein, C. J.(1999). An antiviral mechanism of nitric oxide: inhibition of a viral protease. Immunity 10, 21–28.[CrossRef] [Google Scholar]
  28. Smith, W. L., DeWitt, D. L. & Garavito, R. M.(2000). Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69, 145–182.[CrossRef] [Google Scholar]
  29. Steer, S. A. & Corbett, J. A.(2003). The role and regulation of COX-2 during viral infection. Viral Immunol 16, 447–460.[CrossRef] [Google Scholar]
  30. Steer, S. A., Moran, J. M., Maggi, L. B., Jr, Buller, R. M., Perlman, H. & Corbett, J. A.(2003). Regulation of cyclooxygenase-2 expression by macrophages in response to double-stranded RNA and viral infection. J Immunol 170, 1070–1076.[CrossRef] [Google Scholar]
  31. Steer, S. A., Moran, J. M., Christmann, B. S., Maggi, L. B., Jr & Corbett, J. A.(2006). Role of MAPK in the regulation of double-stranded RNA- and encephalomyocarditis virus-induced cyclooxygenase-2 expression by macrophages. J Immunol 177, 3413–3420.[CrossRef] [Google Scholar]
  32. Stovall, S. H., Yi, A. K., Meals, E. A., Talati, A. J., Godambe, S. A. & English, B. K.(2004). Role of vav1- and src-related tyrosine kinases in macrophage activation by CpG DNA. J Biol Chem 279, 13809–13816.[CrossRef] [Google Scholar]
  33. Suh, H. S., Kim, M. O. & Lee, S. C.(2005). Inhibition of granulocyte–macrophage colony-stimulating factor signaling and microglial proliferation by anti-CD45RO: role of Hck tyrosine kinase and phosphatidylinositol 3-kinase/Akt. J Immunol 174, 2712–2719.[CrossRef] [Google Scholar]
  34. Sun, Y., Huang, J., Xiang, Y., Bastepe, M., Juppner, H., Kobilka, B. K., Zhang, J. J. & Huang, X. Y.(2007). Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR. EMBO J 26, 53–64.[CrossRef] [Google Scholar]
  35. Thomas, S. M. & Brugge, J. S.(1997). Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 13, 513–609.[CrossRef] [Google Scholar]
  36. Tomkowicz, B., Lee, C., Ravyn, V., Cheung, R., Ptasznik, A. & Collman, R. G.(2006). The Src kinase Lyn is required for CCR5 signaling in response to MIP-1β and R5 HIV-1 gp120 in human macrophages. Blood 108, 1145–1150.[CrossRef] [Google Scholar]
  37. Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S. & Fujita, T.(2004). The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5, 730–737.[CrossRef] [Google Scholar]
  38. Ziegler, S. F., Wilson, C. B. & Perlmutter, R. M.(1988). Augmented expression of a myeloid-specific protein tyrosine kinase gene (hck) after macrophage activation. J Exp Med 168, 1801–1810.[CrossRef] [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.022665-0
Loading
/content/journal/jgv/10.1099/vir.0.022665-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error