Selective regulation of interleukin-10 production via Janus kinase pathway in murine conventional dendritic cells

Cell Immunol. 2009;258(1):9-17. doi: 10.1016/j.cellimm.2009.03.006. Epub 2009 Apr 9.

Abstract

In this study, we examined the role of JAKs in regulation of inflammatory versus anti-inflammatory cytokine balance in murine conventional dendritic cells (DCs). Highly purified lipopolysaccharide (upLPS) combined with imiquimod (IQ) synergistically induced IL-10 production by DCs, while each ligand alone showed a slight effect on the IL-10 production. Marked phosphorylation of JAK2, STAT1 and STAT3 was detected in DCs following upLPS plus IQ stimulation. Blocking the JAK pathway by JAK inhibitor I (JAKi) resulted in significant inhibition of IL-10 production by the DCs. However, JAKi showed negligible effect on the DC production of IL-12, IL-6 and TNF-alpha. JAKi completely blocked the TLR-mediated STATs activation, and attenuated the activation of Akt, a downstream effector of PI3K, in DCs stimulated by upLPS plus IQ. LY294002, a specific inhibitor of PI3K, markedly inhibited the DC production of IL-10. Thus, JAK-PI3K axis appeared to be responsible for the IL-10 production by DCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Aminoquinolines / pharmacology*
  • Animals
  • Biomarkers / metabolism
  • Chromones / pharmacology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology
  • Imiquimod
  • Interleukin-10 / agonists
  • Interleukin-10 / antagonists & inhibitors
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology*
  • Janus Kinases / antagonists & inhibitors
  • Janus Kinases / immunology*
  • Janus Kinases / metabolism
  • Ligands
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinase Kinases / drug effects
  • Mitogen-Activated Protein Kinase Kinases / immunology
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Morpholines / pharmacology
  • NF-kappa B / drug effects
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / drug effects
  • Phosphatidylinositol 3-Kinases / immunology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Phosphorylation / immunology
  • STAT1 Transcription Factor / immunology
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / immunology
  • STAT3 Transcription Factor / metabolism
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism

Substances

  • Adjuvants, Immunologic
  • Aminoquinolines
  • Biomarkers
  • Chromones
  • Enzyme Inhibitors
  • Ligands
  • Lipopolysaccharides
  • Morpholines
  • NF-kappa B
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Stat1 protein, mouse
  • Stat3 protein, mouse
  • Toll-Like Receptors
  • Interleukin-10
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Phosphatidylinositol 3-Kinases
  • Janus Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Imiquimod