Histone deacetylase inhibitors suppress immature dendritic cell's migration by regulating CC chemokine receptor 1 expression

Cell Immunol. 2017 Jun:316:11-20. doi: 10.1016/j.cellimm.2017.02.006. Epub 2017 Feb 28.

Abstract

The modulation of immature dendritic cells (iDCs), which involves processes such as phagocytosis, migration, and maturation, is considered a beneficial research theme. Once activated by an antigen, iDCs turn to mature DCs (mDCs) and migrate towards secondary lymphoid organs, and initiate the progress of cellular immunity. Histone deacetylase inhibitors (HDACis) are also thought to be a major modulator of cellular immunity. Herein, we demonstrate that HDACis (trichostatin-A (TSA), sodium butylate (SB), scriptaid (ST)) play a central regulatory role in the migratory activity of iDCs. In our results, TSA, SB and ST showed the potent inhibitory effect on the migration of iDCs stimulated by MIP-1α. The inhibitory activities of HDACis were found to be caused by reduction of CCR1 expression on the cell surface, and by the inhibition of 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).

Keywords: CCR1; Cell migration; HDAC inhibitor; Immature dendritic cell; MIP-1α.

MeSH terms

  • Animals
  • Butyric Acid / pharmacology
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Chemokine CCL3 / pharmacology
  • Dendritic Cells* / cytology
  • Dendritic Cells* / drug effects
  • Dendritic Cells* / immunology
  • Down-Regulation
  • Histone Deacetylase Inhibitors / pharmacology*
  • Hydroxamic Acids / pharmacology
  • Hydroxylamines / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Quinolines / pharmacology
  • Receptors, CCR1 / biosynthesis

Substances

  • Ccl3 protein, mouse
  • Chemokine CCL3
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Hydroxylamines
  • Quinolines
  • Receptors, CCR1
  • scriptaid
  • Butyric Acid
  • trichostatin A