title: Apoptotic cells enhance IL-10 and reduce IL-23 production in human dendritic cells treated with zymosan.
abstract: Contact of apoptotic cells (AC) with phagocytes tilts the balance of pro-inflammatory and anti-inflammatory cytokines. To address the cell- and stimulus-dependency of this mechanism, human monocyte-derived dendritic cells were treated with Jurkat AC in the presence and absence of different stimuli. AC reduced the production of IL-23 and enhanced the production of IL-10 elicited by zymosan, but they did not influence IL-12 p70 production nor did they modify the effect of LPS. Since formation of lipid bodies (LB) and PGE(2) production have been associated with IL-10 induction, the effect of PGE(2), the formation of LB, and the role of PPAR-γ were assessed. Exogenous PGE(2) enhanced IL-10 expression, but no evidence of PGE(2) production elicited by AC was obtained. Inhibition of PPAR-γ activity reduced the production of IL-10 both in the presence and in the absence of AC, but formation of LB in response to zymosan and AC was not observed. Notably, AC induced a transient nuclear translocation of both the CREB coactivator CRTC2/TORC2 and the homeodomain protein PBX1, which are involved in the CREB/HOX/PBX/MEIS transcription complex. These data show a selective effect of AC on the production of cytokines elicited by the fungal surrogate zymosan through the enhancement of CREB-dependent transcription.
authors.affiliation: Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Valladolid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Municio
authors.forename: Etzel
authors.initials: E
authors.lastname: Hugo
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Alvarez
authors.forename: Sara
authors.initials: S
authors.lastname: Alonso
authors.forename: Lydia
authors.initials: L
authors.lastname: Blanco
authors.forename: Nieves
authors.initials: N
authors.lastname: Fernández
authors.forename: Mariano
authors.initials: M
authors.lastname: Sánchez Crespo
mesh_terms: D000946:Antigens, Fungal / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D053759:Interleukin-23 / Q000096:biosynthesis* / Q000276:immunology; D019169:Jurkat Cells; D015398:Signal Transduction / Q000276:immunology; D015054:Zymosan / Q000276:immunology
chemical_list: D000946:Antigens, Fungal; D017362:Cyclic AMP Response Element-Binding Protein; D053759:Interleukin-23; D016753:Interleukin-10; D015054:Zymosan