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Modulation of TNFSR55 and TNFSR75 by cytokines and growth factors in human synovial fibroblasts.
- Source :
-
The Journal of rheumatology. Supplement [J Rheumatol Suppl] 1995 Feb; Vol. 43, pp. 115-9. - Publication Year :
- 1995
-
Abstract
- Tumor necrosis factor alpha (TNF alpha) is suggested to be of importance in the pathogenesis of inflammatory diseases. One mechanism that modulates the action of TNF is binding to specific soluble receptors. Using human synovial fibroblasts, we investigated the effect of cytokines and growth factors, known to be present in increased amounts in arthritic disorders, on the release of the TNF soluble receptors TNFsR75 and TNFsR55. Levels of TNFsR75 and TNFsR55 were determined using conditioned medium from human synovial fibroblasts incubated in increasing concentrations of cytokines, IL-1 beta, TNF alpha, IL-6, and IL-2, and platelet derived growth factor BB (PDGF-BB), transforming growth factor beta (TGF beta), and insulin like growth factor I (IGF-I), alone or in combination with IL-1 beta. The levels of both TNFsR were measured by specific immunoassays. Both TNFsR demonstrated similar levels under basal conditions. IL-1 and TNF alpha induced a significant enhancement of TNFsR75 compared to TNFsR55. When cells were treated with both IL-1 beta and TNF alpha, a marked inhibition in the release of TNFsR55 was observed, while TNFsR75 did not show any changes. IL-6 and IL-2 produced no effect on the release of TNFsR75 and a minimal increase of TNFsR55. PDGF-BB and IGF-I demonstrated a dose dependent increased level of TNFsR55, and both soluble receptors released were inhibited by TGF beta. TGF beta and IL-1 beta together produced a greater inhibition of the release of the TNFsR. These data support the notion that both TNFR in synovial fibroblasts are differently regulated.
- Subjects :
- Antigens, CD drug effects
Becaplermin
Cells, Cultured
Fibroblasts drug effects
Fibroblasts metabolism
Humans
Insulin-Like Growth Factor I pharmacology
Interleukin-1 pharmacology
Interleukin-2 pharmacology
Interleukin-6 pharmacology
Platelet-Derived Growth Factor pharmacology
Proto-Oncogene Proteins c-sis
Receptors, Tumor Necrosis Factor drug effects
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Synovial Membrane cytology
Transforming Growth Factor beta pharmacology
Tumor Necrosis Factor-alpha pharmacology
Antigens, CD biosynthesis
Cytokines pharmacology
Growth Substances pharmacology
Receptors, Tumor Necrosis Factor biosynthesis
Synovial Membrane metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0380-0903
- Volume :
- 43
- Database :
- MEDLINE
- Journal :
- The Journal of rheumatology. Supplement
- Publication Type :
- Academic Journal
- Accession number :
- 7752113