Interleukin-25 fails to activate STAT6 and induce alternatively activated macrophages.
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.
Stolfi
Carmine
C
Department of Internal Medicine, University of Tor Vergata, Rome, Italy.
Caruso
Roberta
R
Franzè
Eleonora
E
Sarra
Massimiliano
M
De Nitto
Daniela
D
Rizzo
Angelamaria
A
Pallone
Francesco
F
Monteleone
Giovanni
G
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*
D020381:Interleukin-17; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human