2-1OAS TSLP downregulates human -defensin 2 through STAT3-dependent pathway in keratinocytes

Wednesday, 14 October 2015: 13:30 - 13:45
Room R1 ABC (Floor 3) (Coex Convention Center)

Sang Wook Son, MD , Dermatology, Korea University, Seoul, South Korea

TSLP downregulates human β-defensin 2 through STAT3-dependent pathway in keratinocytes

Department of Dermatology, Korea University College of Medicine

 Atopic dermatitis (AD) is a chronic and pruritic inflammatory skin disease associated with a defective skin barrier and a dysregulation of Th2 immune response. Most patients with AD show reduced expression of antimicrobial peptides (AMPs), which may plays an important role in host defense against bacteria, fungi, and viruses infection. Thymic stromal lymphopoietin (TSLP) has a pathogenetic role in the initiation and maintenance of allergic inflammatory diseases including AD. The function of TSLP was revealed in previous studies. However, it remains unknown that the regulatory mechanism of HBD-2 expression by TSLP in primary human keratinocytes. 

 The present study demonstrates dose-dependent decreases of human β-defensin-2 (HBD-2) mRNA and protein levels in keratinocytes following stimulation to TSLP. In addition, this study demonstrated the effect of TSLP on HBD-2 expression in human skin equivalent models. We further investigated the regulatory mechanisms of TSLP-reduced HBD-2 expression in primary human keratinocytes. TSLP induced STAT-3 protein expression in primary human keratinocytes. Data from immunohistochemical stain for skin lesions of atopic patients demonstrated the increased expression of STAT-3 than normal skin. HBD-2 was regulated through STAT-3-dependent pathway in keratinocytes. Our results from chromatin immunoprecipitation (ChIP) assay and electrophoretic mobility shift assay (EMSA) showed the direct regulation of TSLP on HBD-2 promoter.

 Taken together, this study reveals that TSLP stimulation may reduce HBD-2 expression through a STAT–3 dependent mechanism in human keratinocytes. The present study suggests a novel and key role of STAT-3 in TSLP-mediated immune response in keratinocytes. Moreover, it would be helpful for understanding the pathologic signal transduction in AD.