Effect of Activating Transcription Factor 3 on Inflammatory Response and Differentiation of Keratinocytes / 대한피부과학회지

ABSTRACT

Background@#Pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune responses. Genetic background is one of the most important factors in disease pathogenesis. However, psoriasis-associated genes have not yet been fully identified. Activating transcription factor 3 (ATF3) is a member of the cyclic adenosine monophosphate responsive element-binding protein family of transcription factors, which may regulate epidermal keratinocytes. @*Objective@#We aimed to evaluate the effects of ATF3 on inflammation and differentiation of keratinocytes. @*Methods@#We evaluated the expression of ATF3 in polyinosinic:polycytidylic acid (poly[I:C])-treated keratinocytes. Subsequently, we compared ATF3 levels in psoriatic and normal skin using immunohistochemical staining. To illustrate the role of ATF3, we generated ATF3-overexpressing keratinocytes and ATF3-knockdown keratinocytes using a recombinant adenovirus. We investigated inflammation and differentiation of keratinocytes by measuring the mRNA levels of inflammatory cytokines and differentiation markers. @*Results@#Treatment of keratinocytes with poly(I:C) increased ATF3 expression in a time-dependent manner. Immunohistochemical staining showed that ATF3 expression was increased in the epidermis of psoriatic tissues. When ATF3 was overexpressed in keratinocytes using a recombinant adenovirus, poly(I:C)-induced inflammation was reduced. Conversely, ATF3 knockdown increased poly(I:C)-induced inflammation. Thus, ATF3 overexpression inhibited keratinocyte differentiation, while ATF3 knockdown promoted it. @*Conclusion@#ATF3 may be involved in the pathogenesis of psoriasis by influencing the inflammatory response and differentiation of keratinocytes.