We assessed expression of IL-20 and its receptors in psoriasis,given the recent implication of IL-20 in epidermal hyperplasia.Psoriatic lesional(LS)skin consistently expressed more IL-20 mRNA than nonlesional(NL)skin....We assessed expression of IL-20 and its receptors in psoriasis,given the recent implication of IL-20 in epidermal hyperplasia.Psoriatic lesional(LS)skin consistently expressed more IL-20 mRNA than nonlesional(NL)skin.Immunoreactivity to IL-20 protein was greater in LS tissue and mainly localized to infiltrating CD68+/CD11c+(myeloid-derived)dermal leukocytes.Because this contrasted with earlier reports of a keratinocyte source,we assessed IL-20 mRNA expression in a variety of cells in vitro,and confirmed a myeloid-derived cellular source(monocytes).Plastic adhesion,activation of β2 integrins,and incubation with tumor necrosis factor-αstimulated expression in these cells.IL-20 receptor(IL-20R)αand IL-20RβmRNA was decreased in LS versus NL skin,which also contrasted with earlier findings.To investigate the relationship between IL-20 and disease activity,we examined psoriasis patients treated with the CD2-targeted agent alefacept.In therapeutic responders,lesional IL-20 mRNA decreased to NL levels,suggesting that CD2+leukocytes may proximally regulate IL-20.Finally,to assess IL-20 function,we used microarrays to screen IL-20-treated keratinocytes,which demonstrated upregulation of disease-related and IFN-γ-induced genes.Hence,IL-20 may influence inflammation through IFN-like effects.Together,these data indicate that IL-20 may be an important effector cytokine in psoriasis,and that its inhibition may represent a potential therapeutic target.展开更多
文摘We assessed expression of IL-20 and its receptors in psoriasis,given the recent implication of IL-20 in epidermal hyperplasia.Psoriatic lesional(LS)skin consistently expressed more IL-20 mRNA than nonlesional(NL)skin.Immunoreactivity to IL-20 protein was greater in LS tissue and mainly localized to infiltrating CD68+/CD11c+(myeloid-derived)dermal leukocytes.Because this contrasted with earlier reports of a keratinocyte source,we assessed IL-20 mRNA expression in a variety of cells in vitro,and confirmed a myeloid-derived cellular source(monocytes).Plastic adhesion,activation of β2 integrins,and incubation with tumor necrosis factor-αstimulated expression in these cells.IL-20 receptor(IL-20R)αand IL-20RβmRNA was decreased in LS versus NL skin,which also contrasted with earlier findings.To investigate the relationship between IL-20 and disease activity,we examined psoriasis patients treated with the CD2-targeted agent alefacept.In therapeutic responders,lesional IL-20 mRNA decreased to NL levels,suggesting that CD2+leukocytes may proximally regulate IL-20.Finally,to assess IL-20 function,we used microarrays to screen IL-20-treated keratinocytes,which demonstrated upregulation of disease-related and IFN-γ-induced genes.Hence,IL-20 may influence inflammation through IFN-like effects.Together,these data indicate that IL-20 may be an important effector cytokine in psoriasis,and that its inhibition may represent a potential therapeutic target.
