Up-regulation of interleukin-13 receptor α1 on human keratinocytes in the skin of psoriasis and atopic dermatitis

Abstract

Background: Interleukin (IL)-13 is a pleiotropic cytokine, which shares many biological functions with IL-4. The receptor subunits of IL-13 consist of IL-4Rα, IL-13Rα1 and IL-13Rα2. The regulatory mechanisms of the IL-13Rα expression in the keratinocytes of certain skin disease have not been known. Objective: To clear the roles of IL-13 and the regulatory mechanisms of its receptor in atopic dermatitis (AD) and psoriasis. Method: The expression of IL-13Rα1 in the skin of AD and psoriasis was investigated by immunohistochemistry. The regulation of IL-13Rα mRNA in the skin and human primary keratinocyte (HPK) was investigated by quantitative PCR. The secretion of IL-6 and RANTES from HPK was measured by ELISA. Results: The expression of IL-13Rα1 was more prominent on the suprabasal keratinocytes in the skin of AD and striking increase of staining was observed on all layers of keratinocyte in the skin of psoriasis. The mRNA of IL-13Rα1, but not of IL-13Rα2 was overexpressed in both skin of AD and psoriasis. In vitro experiment using HPK demonstrated that IFN-γ, IL-13 but not IL-4 could up-regulate the mRNA expression of IL-13Rα1. In contrast, IL-13Rα2 mRNA expression was up-regulated by IFN-γ plus IL-4. Furthermore, the stimulation of HPK with IFN-γ plus IL-13 and/or IL-4 resulted in significant enhancement of IL-6 and RANTES secretion. Conclusion: These findings indicate that IL-4 and IL-13 have different regulatory effects on the expression of IL-13Rα1 and α2, and the overexpression of IL-13Rα1 may play some roles in the pathogenesis of chronic stage of AD or psoriasis.