Histone deacetylase inhibitors suppress CXCR4-mediated dendritic cell migration by regulation of maturation process

Cell Immunol. 2013 Jul-Aug;284(1-2):139-45. doi: 10.1016/j.cellimm.2013.07.014. Epub 2013 Aug 2.

Abstract

Once activated by an infected pathogen, dendritic cells (DC's) migrate toward secondary lymphoid organs, and release inflammatory mediators. Therefore, in some case, mature DC's (mDC's) are considered to be potent inflammatory inducers. In this study we demonstrated that histone acetylation plays an important regulatory role in conserving the migration activity of the DC's. We showed that histone deacetylase (HDAC) inhibition reduces CXC chemokine receptor 4 (CXCR4)-dependent DC's migration. These inhibitory effects were found to be caused by a reduction in the expression of CXCR4, and by the phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 (ERK 1/2), and c-Jun N-terminal kinase (JNK). Taken together, histone deacetylase inhibitors (HDACi's) inhibit the phosphorylation of MAP kinases, and this inhibition reduces the expression of CXCR4, and this reduction decreases the chemotactic activity of mDC's.

Keywords: CXCR4; Cell migration; Dendritic cell; HDAC inhibitor; Inflammation; SDF-1α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Movement / drug effects*
  • Cell Movement / immunology
  • Cell Survival / immunology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / enzymology
  • Dendritic Cells / immunology
  • Histone Deacetylase Inhibitors / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / immunology*
  • Phosphorylation
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / immunology

Substances

  • Histone Deacetylase Inhibitors
  • Receptors, CXCR4
  • Mitogen-Activated Protein Kinases