help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow A correction has been published
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bárdos, T.
Right arrow Articles by Glant, T. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bárdos, T.
Right arrow Articles by Glant, T. T.
(American Journal of Pathology. 2001;159:1711-1721.)
© 2001 American Society for Investigative Pathology

Regular Articles

Anti-Inflammatory and Chondroprotective Effect of TSG-6 (Tumor Necrosis Factor-{alpha}-Stimulated Gene-6) in Murine Models of Experimental Arthritis

Tamás Bárdos*, Rajesh V. Kamath{dagger}, Katalin Mikecz*{dagger} and Tibor T. Glant*{dagger}

From the Departments of Orthopedic Surgery*
and Biochemistry,{dagger}
Section of Biochemistry and Molecular Biology, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, Illinois

Tumor necrosis factor-{alpha} (TNF-{alpha})-stimulated gene-6 (TSG-6) is up-regulated by various cytokines and growth factors. TSG-6 binds to hyaluronan in inflamed synovial tissue and forms a complex with a serine protease inter-{alpha}-trypsin inhibitor (I{alpha}I), increasing the protease inhibitory effect of I{alpha}I >100-fold. The TSG-6/I{alpha}I complex then blocks serine proteases, including the plasminogen-plasmin activation, probably the most important component in the activation processes of matrix metalloproteinases. To gain insight into the mechanisms of TSG-6 action in arthritis, we have used an autoimmune murine model (proteoglycan-induced arthritis) for systemic, and a monoarticular form of arthritis (antigen-induced arthritis) for local treatment of arthritis with recombinant mouse TSG-6 (rmTSG-6). Intravenous injection of rmTSG-6 induced a dramatic reduction of edema in acutely inflamed joints by immobilizing CD44-bound hyaluronan and, in long-term treatment, protected cartilage from degradation and blocked subchondral and periosteal bone erosion in inflamed joints. The intra-articular injection of a single dose (100 µg) of rmTSG-6 exhibited a strong chondroprotective effect for up to 5 to 7 days, preventing cartilage proteoglycan from metalloproteinase-induced degradation. In contrast, rmTSG-6 did not postpone the onset, nor reduce the incidence of arthritis. We were unable to detect any significant differences between control and rmTSG-6-treated animals when various serum markers (including pro- and anti-inflammatory cytokines, auto- and heteroantibody productions) or antigen-specific T-cell responses were compared, nor when the expressions of numerous cell surface receptors or adhesion molecules were measured. TSG-6 seems to play a critical negative regulatory feed-back function in inflammation, especially in arthritic processes.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
G. E. Garcia, H.-G. Wisniewski, M. S. Lucia, N. Arevalo, T. J. Slaga, S. L. Kraft, R. Strange, and A. P. Kumar
2-Methoxyestradiol Inhibits Prostate Tumor Development in Transgenic Adenocarcinoma of Mouse Prostate: Role of Tumor Necrosis Factor-{alpha}-Stimulated Gene 6
Clin. Cancer Res., February 1, 2006; 12(3): 980 - 988.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. A. Kuznetsova, A. J. Day, D. J. Mahoney, M. S. Rugg, D. F. Mosher, and D. D. Roberts
The N-terminal Module of Thrombospondin-1 Interacts with the Link Domain of TSG-6 and Enhances Its Covalent Association with the Heavy Chains of Inter-{alpha}-trypsin Inhibitor
J. Biol. Chem., September 2, 2005; 280(35): 30899 - 30908.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. J. Mahoney, B. Mulloy, M. J. Forster, C. D. Blundell, E. Fries, C. M Milner, and A. J. Day
Characterization of the Interaction between Tumor Necrosis Factor-stimulated Gene-6 and Heparin: IMPLICATIONS FOR THE INHIBITION OF PLASMIN IN EXTRACELLULAR MATRIX MICROENVIRONMENTS
J. Biol. Chem., July 22, 2005; 280(29): 27044 - 27055.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
T Bardos, Z Szabo, M Czipri, C Vermes, M Tunyogi-Csapo, R M Urban, K Mikecz, and T T Glant
A longitudinal study on an autoimmune murine model of ankylosing spondylitis
Ann Rheum Dis, July 1, 2005; 64(7): 981 - 987.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H.-G. Wisniewski, E. S. Snitkin, C. Mindrescu, M. H. Sweet, and J. Vilcek
TSG-6 Protein Binding to Glycosaminoglycans: FORMATION OF STABLE COMPLEXES WITH HYALURONAN AND BINDING TO CHONDROITIN SULFATES
J. Biol. Chem., April 15, 2005; 280(15): 14476 - 14484.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Lesley, I. Gal, D. J. Mahoney, M. R. Cordell, M. S. Rugg, R. Hyman, A. J. Day, and K. Mikecz
TSG-6 Modulates the Interaction between Hyaluronan and Cell Surface CD44
J. Biol. Chem., June 11, 2004; 279(24): 25745 - 25754.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Szanto, I. Gal, A. Gonda, T. T. Glant, and K. Mikecz
Expression of L-Selectin, but Not CD44, Is Required for Early Neutrophil Extravasation in Antigen-Induced Arthritis
J. Immunol., June 1, 2004; 172(11): 6723 - 6734.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
C. M. Milner and A. J. Day
TSG-6: a multifunctional protein associated with inflammation
J. Cell Sci., May 15, 2003; 116(10): 1863 - 1873.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
C. Fulop, S. Szanto, D. Mukhopadhyay, T. Bardos, R. V. Kamath, M. S. Rugg, A. J. Day, A. Salustri, V. C. Hascall, T. T. Glant, et al.
Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice
Development, May 15, 2003; 130(10): 2253 - 2261.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. A. Ochsner, D. L. Russell, A. J. Day, R. M. Breyer, and J. S. Richards
Decreased Expression of Tumor Necrosis Factor-{alpha}-Stimulated Gene 6 in Cumulus Cells of the Cyclooxygenase-2 and EP2 Null Mice
Endocrinology, March 1, 2003; 144(3): 1008 - 1019.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
L. L. Espey and J. S. Richards
Temporal and Spatial Patterns of Ovarian Gene Transcription Following an Ovulatory Dose of Gonadotropin in the Rat
Biol Reprod, December 1, 2002; 67(6): 1662 - 1670.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Lesley, N. M. English, I. Gal, K. Mikecz, A. J. Day, and R. Hyman
Hyaluronan Binding Properties of a CD44 Chimera Containing the Link Module of TSG-6
J. Biol. Chem., July 12, 2002; 277(29): 26600 - 26608.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. A. Nentwich, Z. Mustafa, M. S. Rugg, B. D. Marsden, M. R. Cordell, D. J. Mahoney, S. C. Jenkins, B. Dowling, E. Fries, C. M. Milner, et al.
A Novel Allelic Variant of the Human TSG-6 Gene Encoding an Amino Acid Difference in the CUB Module. CHROMOSOMAL LOCALIZATION, FREQUENCY ANALYSIS, MODELING, AND EXPRESSION
J. Biol. Chem., May 3, 2002; 277(18): 15354 - 15362.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by the American Society for Investigative Pathology.