Abstract
Interleukin-1β (IL-1β), a key-cytokine in osteoarthritis, impairs TGFβ signaling through TβRII down-regulation by increasing its degradation. Here, we investigated the molecular mechanism that controls TßRII fate in IL-1ß treated cells. Chondrocytes were treated with IL-1ß in the presence of different inhibitors. TßRII and Cav-1 expression were assayed by Western blot and RT-PCR. We showed that IL-1ß-induced degradation of TßRII is dependent on proteasome and on its internalization in caveolae. In addition, IL-1ß enhances Cav-1 expression, a major constituent of lipid raft. In conclusion, we enlighten a new mechanism by which IL-1ß antagonizes TGFß pathway and propose a model of TßRII turnover regulation upon IL-1ß treatment.
Copyright © 2012 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Biological Transport / drug effects
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Boronic Acids / pharmacology
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Bortezomib
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Caveolae / metabolism
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Caveolin 1 / metabolism
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Cells, Cultured
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Chondrocytes / drug effects*
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Chondrocytes / metabolism*
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Humans
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Interleukin-1beta / pharmacology*
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Lysosomes / drug effects
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Lysosomes / metabolism
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Middle Aged
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Nystatin / pharmacology
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Proteasome Endopeptidase Complex / metabolism
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Proteasome Inhibitors
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Protein Serine-Threonine Kinases / metabolism*
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Proteolysis / drug effects*
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Pyrazines / pharmacology
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / metabolism*
Substances
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Boronic Acids
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Caveolin 1
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Interleukin-1beta
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Proteasome Inhibitors
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Pyrazines
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Receptors, Transforming Growth Factor beta
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Nystatin
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Bortezomib
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II
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Proteasome Endopeptidase Complex