TSG-6: a TNF-, IL-1-, and LPS-inducible secreted glycoprotein associated with arthritis.
TSG-6 (TNF-stimulated gene 6) was originally discovered by differential screening of a cDNA library prepared from TNF-stimulated human diploid FS-4 fibroblasts. We show that the 35-kDa protein encoded by TSG-6 was undetectable in the medium of untreated FS-4 cultures, whereas its production reached approximately 1400 and 700 ng/10(6) cells after 24-h treatment with IL-1 or TNF, respectively. Stimulation of TSG-6 protein and mRNA levels was also demonstrated in normal human mononuclear cells by treatment with TNF and, especially, by LPS. In view of the inducibility of TSG-6 by inflammatory cytokines and its earlier demonstrated affinity for hyaluronan, we examined the presence of TSG-6 protein in the synovial fluids from patients with various forms of arthritis. TSG-6 protein was undetectable in the joint fluids of persons with no known history of arthritis, but high levels of TSG-6 oere demonstrated in the synovial fluids of a majority of arthritis patients. TSG-6 protein was also detected in the sera of some of the arthritis patients, albeit at concentrations that were less than in the joint fluids. To investigate the source of TSG-6 in the synovial fluids, we examined the production of TSG-6 protein in cultures of synovial cells. Synoviocytes from rheumatoid arthritis patients produced TSG-6 protein constitutively, and this production was increased by treatment with TNF or IL-1, but not with TGF-beta. Steady-state levels of TSG-6 mRNA were also increased in synoviocytes after treatment with TNF or IL-1. The presence of high levels of TSG-6 protein in the synovial fluids of arthritis patients and its inducibility by inflammatory cytokines in fibroblasts, mononuclear cells, synoviocytes, and chondrocytes suggest a role for TSG-6 in arthritis and inflammation.
Wisniewski
H G
HG
Department of Microbiology, NYU Medical Center, NY 10016.
Maier
R
R
Lotz
M
M
Lee
S
S
Klampfer
L
L
Lee
T H
TH
Vilcek
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001168:Arthritis / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis*; D002478:Cells, Cultured; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007596:Joints / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008875:Middle Aged; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; C072273:TNFAIP6 protein, human; D014409:Tumor Necrosis Factor-alpha