Caspases regulate VAMP-8 expression and phagocytosis in dendritic cells

Biochem Biophys Res Commun. 2009 Sep 18;387(2):371-5. doi: 10.1016/j.bbrc.2009.07.028. Epub 2009 Jul 14.

Abstract

During an inflammation and upon encountering pathogens, immature dendritic cells (DC) undergo a maturation process to become highly efficient in presenting antigens. This transition from immature to mature state is accompanied by various physiological, functional and morphological changes including reduction of caspase activity and inhibition of phagocytosis in the mature DC. Caspases are cysteine proteases which play essential roles in apoptosis, necrosis and inflammation. Here, we demonstrate that VAMP-8, (a SNARE protein of the early/late endosomes) which has been shown previously to inhibit phagocytosis in DC, is a substrate of caspases. Furthermore, we identified two putative conserved caspase recognition/cleavage sites on the VAMP-8 protein. Consistent with the up-regulation of VAMP-8 expression upon treatment with caspase inhibitor (CI), immature DC treated with CI exhibits lower phagocytosis activity. Thus, our results highlight the role of caspases in regulating VAMP-8 expression and subsequently phagocytosis during maturation of DC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caspase Inhibitors
  • Caspases / metabolism*
  • Cell Line
  • Dendritic Cells / immunology*
  • Lipopolysaccharides / immunology
  • Mice
  • Molecular Sequence Data
  • Phagocytosis*
  • R-SNARE Proteins / biosynthesis
  • R-SNARE Proteins / metabolism*
  • Up-Regulation

Substances

  • Caspase Inhibitors
  • Lipopolysaccharides
  • R-SNARE Proteins
  • Vamp8 protein, mouse
  • Caspases