PMID- 11696432
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20220311
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 159
IP  - 5
DP  - 2001 Nov
TI  - Anti-inflammatory and chondroprotective effect of TSG-6 (tumor necrosis 
      factor-alpha-stimulated gene-6) in murine models of experimental arthritis.
PG  - 1711-21
AB  - 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 (IalphaI), increasing the protease inhibitory effect of IalphaI 
      >100-fold. The TSG-6/IalphaI 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 microg) 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.
FAU - Bardos, T
AU  - Bardos T
AD  - Department of Orthopedic Surgery, Section of Biochemistry and Molecular Biology, 
      Rush University, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 
      60612, USA.
FAU - Kamath, R V
AU  - Kamath RV
FAU - Mikecz, K
AU  - Mikecz K
FAU - Glant, T T
AU  - Glant TT
LA  - eng
GR  - AR45652/AR/NIAMS NIH HHS/United States
GR  - R01 AR040310/AR/NIAMS NIH HHS/United States
GR  - AR40310/AR/NIAMS NIH HHS/United States
GR  - P01 AR045652/AR/NIAMS NIH HHS/United States
GR  - AR47135/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antigens)
RN  - 0 (Biomarkers)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Proteoglycans)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tnfaip6 protein, mouse)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
EIN - Am J Pathol 2002 Mar;160(3):1193
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Antigens/immunology
MH  - Arthritis/complications/*drug therapy/immunology/*pathology
MH  - Autoimmune Diseases/immunology/physiopathology
MH  - Binding Sites
MH  - Binding, Competitive
MH  - Biomarkers
MH  - Cartilage, Articular/*drug effects/*pathology
MH  - Cell Adhesion Molecules/metabolism/*therapeutic use
MH  - Edema/etiology/pathology
MH  - Hyaluronic Acid/metabolism
MH  - Knee Joint/drug effects/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Preventive Medicine/methods
MH  - Proteoglycans/immunology
MH  - Recombinant Proteins/metabolism/therapeutic use
MH  - Time Factors
PMC - PMC1867074
EDAT- 2001/11/07 10:00
MHDA- 2002/01/05 10:01
PMCR- 2002/05/01
CRDT- 2001/11/07 10:00
PHST- 2001/11/07 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/07 10:00 [entrez]
PHST- 2002/05/01 00:00 [pmc-release]
AID - S0002-9440(10)63018-0 [pii]
AID - 2906 [pii]
AID - 10.1016/s0002-9440(10)63018-0 [doi]
PST - ppublish
SO  - Am J Pathol. 2001 Nov;159(5):1711-21. doi: 10.1016/s0002-9440(10)63018-0.