IL ‐33 induces Egr‐1‐dependent TSLP expression via the MAPK pathways in human keratinocytes

Atopic dermatitis ( AD ) is a chronic inflammatory skin disease in which T‐helper type 2 (Th2)‐type immune responses are dominant. Th2 cytokine, interleukin ( IL )‐33 and thymic stromal lymphopoietin ( TSLP ) have been suggested to have an important role in AD . IL ‐33 is highly expressed in AD , but its role in AD has not yet been fully understood. To further identify the role of IL ‐33 in AD , we investigated the expression of TSLP induced by IL ‐33 in keratinocytes. This study revealed that IL ‐33 induced TSLP expression in human keratinocytes. Early growth response protein 1 (Egr)‐1, which is an inflammatory transcriptional factor, is induced by IL ‐33. IL ‐33‐mediated TSLP induction in keratinocytes was suppressed by treatment with mitogen‐activated protein kinase ( MAPK ) inhibitors or small interfering RNA against Egr‐1. Chromatin immunoprecipitation (Ch IP ) assay indicated the direct involvement of Egr‐1 in IL ‐33‐mediated TSLP induction. Taken together, these findings indicate that IL ‐33 may increase TSLP expression through an Egr‐1‐dependent mechanism via ERK 1/2, JNK and p38 activation in keratinocytes. These data suggest that the IL ‐33‐ ERK / JNK /p38/Egr‐1/ TSLP axis is involved in allergic skin Th2 inflammation, and it may be a novel therapeutic target.