title: Interleukin-25 fails to activate STAT6 and induce alternatively activated macrophages.
abstract: Interleukin-25 (IL-25), a T helper type 2 (Th2) -related factor, inhibits the production of inflammatory cytokines by monocytes/macrophages. Since Th2 cytokines antagonize classically activated monocytes/macrophages by inducing alternatively activated macrophages (AAMs), we here assessed the effect of IL-25 on the alternative activation of human monocytes/macrophages. The interleukins IL-25, IL-4 and IL-13 were effective in reducing the expression of inflammatory chemokines in monocytes. This effect was paralleled by induction of AAMs in cultures added with IL-4 or IL-13 but not with IL-25, regardless of whether cells were stimulated with lipopolysaccharide or interferon-γ. Moreover, pre-incubation of cells with IL-25 did not alter the ability of both IL-4 and IL-13 to induce AAMs. Both IL-4 and IL-13 activated signal transducer and activator of transcription 6 (STAT6), and silencing of this transcription factor markedly reduced the IL-4/IL-13-driven induction of AAMs. In contrast, IL-25 failed to trigger STAT6 activation. Among Th2 cytokines, only IL-25 and IL-10 were able to activate p38 mitogen-activated protein kinase. These results collectively indicate that IL-25 fails to induce AAMs and that Th2-type cytokines suppress inflammatory responses in human monocytes by activating different intracellular signalling pathways.
authors.affiliation: Department of Internal Medicine, University of Tor Vergata, Rome, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Stolfi
authors.forename: Roberta
authors.initials: R
authors.lastname: Caruso
authors.forename: Eleonora
authors.initials: E
authors.lastname: Franzè
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Sarra
authors.forename: Daniela
authors.initials: D
authors.lastname: De Nitto
authors.forename: Angelamaria
authors.initials: A
authors.lastname: Rizzo
authors.forename: Francesco
authors.initials: F
authors.lastname: Pallone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monteleone
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human