Regulation of lipopolysaccharide-induced inflammatory response by heat shock protein 27 in THP-1 cells

Cell Immunol. 2010;264(2):127-34. doi: 10.1016/j.cellimm.2010.05.011. Epub 2010 May 27.

Abstract

HSP27 is a member of the small HSP family which has been linked to different signaling pathways regulating critical cellular functions. But the role of HSP27 in LPS-induced inflammatory signaling pathways is still unclear. In the present study, both overexpression and RNA interference experiments indicated that HSP27 increased LPS-induced expression of iNOS and COX-2 and release of NO/PGE2 through enhancing NF-kappaB but not MAPK activation. The effects of HSP27 on LPS-induced iNOS/COX-2 expression and relative signaling cascade were closely related with the phosphorylation of HSP27. Further studies have shown that HSP27-regulated LPS-induced activation of NF-kappaB by interacting with TRAF6 and increasing the association of TRAF6-IKKgamma. This could be a probable mechanism by which HSP27 modulates LPS-induce inflammatory signaling pathways. Thus, HSP27 may play a potential role in regulating inflammatory responses in immunologic system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cloning, Molecular
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Dinoprostone / metabolism
  • HSP27 Heat-Shock Proteins / genetics
  • HSP27 Heat-Shock Proteins / immunology
  • HSP27 Heat-Shock Proteins / metabolism*
  • Humans
  • I-kappa B Kinase / metabolism
  • Inflammation
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / metabolism*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • RNA, Small Interfering / genetics
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • TNF Receptor-Associated Factor 6 / metabolism
  • Transcriptional Activation / genetics
  • Transcriptional Activation / immunology
  • Transgenes / genetics

Substances

  • HSP27 Heat-Shock Proteins
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Small Interfering
  • TNF Receptor-Associated Factor 6
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • I-kappa B Kinase
  • Dinoprostone