Interleukin-6 receptor shedding is enhanced by interleukin-1beta and tumor necrosis factor alpha and is partially mediated by tumor necrosis factor alpha-converting enzyme in osteoblast-like cells.
[en] OBJECTIVE: Interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) activation of gp130 represents an alternative pathway for osteoclast development in inflammatory conditions. The goal of the present study was to investigate changes in sIL-6R levels in response to the inflammatory cytokines IL-1beta and tumor necrosis factor alpha (TNFalpha) and to determine the role of TNFalpha-converting enzyme (TACE) in this process. METHODS: Levels of sIL-6R in the culture media of MG63 and SAOS-2 osteoblast-like cell lines after exposure to various agents were determined by immunoassay. TACE protein levels were measured by Western immunoblotting. Cells were transfected with small interfering RNA (siRNA) or with an expression plasmid for IL-6R and TACE to determine the potential involvement of TACE in IL-6R shedding. RESULTS: IL-1beta and TNFalpha increased the levels of sIL-6R in the culture media of MG63 osteoblast-like cells. This effect was not influenced by cycloheximide or 5,6-dichlorobenzimidazole riboside but was markedly inhibited by the calcium chelator EGTA and by the TACE and matrix metalloproteinase inhibitor hydroxamate (Ru36156). IL-1beta and TNFalpha had no influence on the alternatively spliced form of IL-6R RNA. Levels of sIL-6R were reduced when MG63 cells were transiently transfected with TACE siRNA. Transfection of SAOS-2 cells with expression plasmids for IL-6R and TACE produced a dose-dependent increase in sIL-6R levels. CONCLUSION: IL-1beta- and TNFalpha-mediated induction of IL-6R shedding in osteoblast-like cells is at least partly dependent on TACE activation.
Research center :
Giga-Signal Transduction - ULiège
Disciplines :
Rheumatology
Author, co-author :
Franchimont, Nathalie
Lambert, Cécile ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Huynen, Pascale ; Centre Hospitalier Universitaire de Liège - CHU > Microbiologie médicale
Ribbens, Clio ; Centre Hospitalier Universitaire de Liège - CHU > Rhumatologie
Relic, Biserka ; Centre Hospitalier Universitaire de Liège - CHU > Rhumatologie
Chariot, Alain ; Centre Hospitalier Universitaire de Liège - CHU > Chimie médicale
Bours, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
Piette, Jacques ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie - Département des sciences de la vie - GIGA-Research
Merville, Marie-Paule ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Malaise, Michel ; Centre Hospitalier Universitaire de Liège - CHU > Rhumatologie
Language :
English
Title :
Interleukin-6 receptor shedding is enhanced by interleukin-1beta and tumor necrosis factor alpha and is partially mediated by tumor necrosis factor alpha-converting enzyme in osteoblast-like cells.
Publication date :
2005
Journal title :
Arthritis and Rheumatism
ISSN :
0004-3591
eISSN :
1529-0131
Publisher :
Wiley Liss, Inc., New York, United States - New York
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