Induction of interleukin-10 expression through Fcalpha receptor in human monocytes and monocyte-derived dendritic cells: role of p38 MAPKinase.
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.
Pilette
Charles
C
Laboratory of Allergy & Mucosal Immunology (Research Pole of Pneumology, ENT and Dermatology) and Cliniques Universitaires St-Luc, Université catholique de Louvain (UCL), Brussels, Belgium. charles.pilette@uclouvain.be
Detry
Bruno
B
Guisset
Amélie
A
Gabriels
Julie
J
Sibille
Yves
Y
D015153:Blotting, Western; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D011961:Receptors, Fc / Q000187:drug effects / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
D004791:Enzyme Inhibitors; D007070:Immunoglobulin A; D011961:Receptors, Fc; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases