Induction of the IL-10 gene via the fas receptor in monocytes--an anti-inflammatory mechanism in the absence of apoptosis.
Death receptors play an important role in controlling cell numbers and immune responses. In contrast to TNF receptors, little is known about non-apoptosis functions of the Fas receptor (CD95, APO-1). Here we demonstrate that Fas receptor engagement results in the induction of the IL-10 gene in monocytes, but not in lymphocytes or dendritic cells. In contrast, TNF-alpha stimulated IL-10 production in dendritic cells but not monocytes. Fas receptor-mediated transcriptional activation of the IL-10 gene was followed by the release of large amounts of the cytokine in cell cultures and occurred in the absence of apoptosis induction. Since caspase activation did not occur in monocytes following Fas receptor engagement, it is unlikely that caspases are involved in IL-10 gene activation. Monocyte-derived IL-10 suppressed T cell proliferation induced by anti-CD3 monoclonal antibody without affecting CD3-mediated transmembrane signal transduction. In conclusion, we report about a novel pathway initiated via the Fas receptor leading to transcriptional activation of at least one cytokine gene. Fas ligand-induced IL-10 production in monocytes might represent an important anti-inflammatory mechanism in secondary immune responses.
Daigle
I
I
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos.
Rückert
B
B
Schnetzler
G
G
Simon
H U
HU
D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology; D020169:Caspases / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016853:Muromonab-CD3 / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019014:fas Receptor / Q000187:drug effects / Q000502:physiology*
D017252:CD3 Complex; D016853:Muromonab-CD3; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D016753:Interleukin-10; D020169:Caspases