Induction of interleukin-10 expression through Fcalpha receptor in human monocytes and monocyte-derived dendritic cells: role of p38 MAPKinase

Immunol Cell Biol. May-Jun 2010;88(4):486-93. doi: 10.1038/icb.2009.120. Epub 2010 Jan 19.

Abstract

As previously reported by others for immunoglobulin (Ig)G, we observed that IgA can induce interleukin (IL)-10 expression in human monocytes. In this study, we explored the molecular mechanisms of IL-10 induction by IgA in monocytes and monocyte-derived dendritic cells (MD-DCs). Monomeric IgA induced IL-10 production in monocytes and this production was further increased upon IgA cross-linking. Similar IL-10 responses were observed in monocytes and autologous MD-DCs, and were inhibited (by approximately 77%) by preincubation with a blocking mAb to FcalphaRI. IL-10 induction by IgA correlated with activation of MAPKinases ERK1/2, p38 and JNK, whereas only p38-inhibitor SB-203580 inhibited IL-10 induction. Upon IgA stimulation, AP-1, NFkappaB and Sp1 transcription factors were activated and inhibitors of NFkappaB and of Sp1 suppressed IgA-driven transcriptional activation of IL-10. In addition, p38 MAPK activation appeared that it was required to control nuclear translocation of NFkappaB and Sp1 upon IgA stimulation. Therefore, in human monocytes and MD-DCs the mechanisms of IL-10 induction by IgA involve p38 MAPK-dependent recruitment of both NFkappaB and Sp1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Dendritic Cells / drug effects
  • Dendritic Cells / enzymology
  • Dendritic Cells / immunology*
  • Dose-Response Relationship, Immunologic
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin A / pharmacology
  • Interleukin-10 / metabolism*
  • Monocytes / drug effects
  • Monocytes / enzymology
  • Monocytes / immunology*
  • Receptors, Fc / drug effects
  • Receptors, Fc / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases / immunology*

Substances

  • Enzyme Inhibitors
  • Immunoglobulin A
  • Receptors, Fc
  • Interleukin-10
  • p38 Mitogen-Activated Protein Kinases