Association of HSP22 with mTOR in osteoblasts: regulation of TNF-α-stimulated IL-6 synthesis

FEBS Lett. 2018 Apr;592(7):1202-1210. doi: 10.1002/1873-3468.13028. Epub 2018 Mar 23.

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.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • HSP20 Heat-Shock Proteins / genetics
  • HSP20 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / genetics
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Molecular Chaperones
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Phosphorylation / drug effects
  • Ribosomal Protein S6 Kinases, 70-kDa / genetics
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • HSP20 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Hspb8 protein, mouse
  • Interleukin-6
  • Molecular Chaperones
  • Muscle Proteins
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • mTOR protein, mouse
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 1