title: Interleukin-4 can induce interleukin-4 production in dendritic cells.
abstract: The presence of interleukin-4 (IL-4) during the generation of dendritic cells (DC) from precursor cells results in measurable increases of IL-12 in supernatants but IL-4 secretion has not been reported. However, DC have IL-4 receptors and are able to make IL-4. We therefore sought evidence for autocrine effects of IL-4 on DC. IL-4 gene expression was low in DC generated from bone-marrow stem cells in the presence of granulocyte-macrophage colony-stimulating factor but was up-regulated by exposure of the developing DC to IL-4. Exposure to IL-4 also induced intracellular IL-4 production in DC. The intracellular IL-4 induced in the presence of IL-4 was increased following further DC maturation with tumour necrosis factor-alpha. By contrast, in supernatants of DC, IL-4 was rarely detected and only at late culture periods. However, after exposure of DC to IL-4, cell-bound IL-4 was detected transiently, which suggested binding and internalization of the cytokine. Binding via IL-4 receptor-alpha was indicated from phosphorylation of the signal transducer and activator of transcription (STAT) protein 6, which is known to mediate IL-4 function. Cytokine persisting within the supernatants of the cells may therefore be unrepresentative of the actual production and function of IL-4 in the cells; IL-4 may be produced in DC in response to exposure to IL-4 but may then be lost from the supernatants during cell binding and activation of the cells.
authors.affiliation: Antigen Presentation Research Group, Imperial College London, UK.
authors.forename: Asher
authors.initials: A
authors.lastname: Maroof
authors.forename: Michelle
authors.initials: M
authors.lastname: Penny
authors.forename: Rosetta
authors.initials: R
authors.lastname: Kingston
authors.forename: Clare
authors.initials: C
authors.lastname: Murray
authors.forename: Sabita
authors.initials: S
authors.lastname: Islam
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Bedford
authors.forename: Stella C
authors.initials: SC
authors.lastname: Knight
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000276:immunology; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000378:metabolism
chemical_list: D016207:Cytokines; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor