Abstract
Heat shock protein 22 (HSP22) is ubiquitously expressed in various types of cells including in osteoblasts. We previously reported that tumor necrosis factor (TNF)-α stimulates interleukin (IL)-6 synthesis via p44/p42 MAPK in osteoblast-like MC3T3-E1 cells and that mTOR/p70 S6 kinase (p70 S6K) negatively regulates the IL-6 synthesis. In this study, we investigated the involvement of HSP22 in TNF-α-stimulated-IL-6 synthesis and the underlying mechanism in MC3T3-E1 cells. HSP22 knockdown reduces TNF-α-stimulated release of IL-6. In addition, HSP22 knockdown strengthens TNF-α-induced phosphorylation of p70 S6K but suppresses that of p44/p42 MAPK. HSP22 coimmunoprecipitates with mTOR. HSP22 knockdown increases the basal levels of phosphorylated mTOR. These results strongly suggest that HSP22 interacts with mTOR and regulates TNF-α-induced IL-6 synthesis in osteoblasts.
Keywords:
mTOR; HSP22; osteoblast.
© 2018 Federation of European Biochemical Societies.
Publication types
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Letter
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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HSP20 Heat-Shock Proteins / genetics
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HSP20 Heat-Shock Proteins / metabolism*
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Heat-Shock Proteins
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Interleukin-6 / biosynthesis*
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Interleukin-6 / genetics
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MAP Kinase Signaling System / drug effects*
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Mice
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Mitogen-Activated Protein Kinase 1 / metabolism
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Molecular Chaperones
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Osteoblasts / cytology
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Osteoblasts / metabolism*
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Phosphorylation / drug effects
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Ribosomal Protein S6 Kinases, 70-kDa / genetics
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Ribosomal Protein S6 Kinases, 70-kDa / metabolism
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism*
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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HSP20 Heat-Shock Proteins
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Heat-Shock Proteins
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Hspb8 protein, mouse
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Interleukin-6
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Molecular Chaperones
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Muscle Proteins
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Tumor Necrosis Factor-alpha
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interleukin-6, mouse
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mTOR protein, mouse
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Ribosomal Protein S6 Kinases, 70-kDa
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TOR Serine-Threonine Kinases
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Mitogen-Activated Protein Kinase 1