International Immunology, Vol. 16, No. 3, pp. 477-488,
March 2004
© 2004 Japanese Society for Immunology
Osteopontin affects the persistence of ß-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms
1 Divison of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan 2 Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854-8082, USA 3 Department of Genetics, Rutgers University, Piscataway, NJ 08855-1059, USA
Correspondence to: T. Uede; E-mail: toshi{at}igm.hokudai.ac.jp
Transmitting editor: S. Koyasu
Osteopontin (OPN) plays a pivotal role in various immune responses and inflammatory diseases. OPN is expressed in various granulomatous diseases; however, the cellular and molecular role of OPN in these diseases is not well known. We analyzed the role of OPN in a ß-glucan-induced hepatic granuloma model. First, we found that neither OPN deficiency nor overexpression of OPN affected the number and the size of hepatic granulomas at day 7, indicating that OPN is not involved in the formation of hepatic granulomas at the early stages. Importantly, OPN did not influence the liver tissue damage as defined by alanine aminotransferase and aspartate aminotransferase levels at early stages. Second, OPN deficiency resulted in the reduction of IL-12 and IFN-
production at early stages. Third, at late stages, OPN deficiency resulted in a decrease in the number and size of hepatic granulomas, and a reduction of liver tissue injury. This was due to the reduction of the cellular recruitment including macrophages, CD4 T cells and dendritic cells into the liver, and the reduction of tumor necrosis factor (TNF)-
production in the liver. In contrast, overexpression of OPN resulted in the persistence of granuloma formation. These data suggest that OPN affects the persistence of hepatic granuloma formation. Our results indicate that OPN up-regulates the production of IL-12 and IFN- within the granulomas at early stages, and OPN has an additional role in the regulation of cellular recruitment and TNF- production at late stages that determine the severity of liver tissue injury.
Keywords: CD4 T cell, dendritic cell, IFN-, IL-12, tumor necrosis factor-
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. K. Ramaiah and S. Rittling Pathophysiological Role of Osteopontin in Hepatic Inflammation, Toxicity, and Cancer Toxicol. Sci., May 1, 2008; 103(1): 4 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hashimoto, D. Sun, S. R. Rittling, D. T. Denhardt, and W. Young Osteopontin-Deficient Mice Exhibit Less Inflammation, Greater Tissue Damage, and Impaired Locomotor Recovery from Spinal Cord Injury Compared with Wild-Type Controls J. Neurosci., March 28, 2007; 27(13): 3603 - 3611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Gregory, E. F. Morand, S. J. McKeown, J. A. Ralph, P. Hall, Y. H. Yang, S. R. McColl, and M. J. Hickey Macrophage Migration Inhibitory Factor Induces Macrophage Recruitment via CC Chemokine Ligand 2 J. Immunol., December 1, 2006; 177(11): 8072 - 8079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Yimin and M. Kohanawa A Regulatory Effect of the Balance between TNF-{alpha} and IL-6 in the Granulomatous and Inflammatory Response to Rhodococcus aurantiacus Infection in Mice J. Immunol., July 1, 2006; 177(1): 642 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sodek, A. P. Batista Da Silva, and R. Zohar Osteopontin and mucosal protection. J. Dent. Res., May 1, 2006; 85(5): 404 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Briese, M. Oberndorfer, C. Patschenik, H. M. Schulte, A. Makrigiannakis, T. Loning, and A.-M. Bamberger Osteopontin Is Colocalized with the Adhesion Molecule CEACAM1 in the Extravillous Trophoblast of the Human Placenta and Enhances Invasion of CEACAM1-Expressing Placental Cells J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5407 - 5413. [Abstract] [Full Text] [PDF]
|
|