The effect of circadian gene, Per2, on JAK-STAT pathway in inflammation model in vitro 3581

Abstract Description Per2 is core circadian gene to generate circadian rhythms and it is associated with enhancing inflammation. JAK-STAT pathway is a classical signal transduction pathway in keratinocytes to initiates skin inflammation through releasing cytokines and chemokines which leads atopic dermatitis. In this study we investigated the role of clock gene Per2 in skin inflammation using HaCaT cells transfected with siPer2 RNA. The transfected and un-transfected HaCaT cells were stimulated with 25 ng of TNF? and IFN?? each for 6 hours. Cell supernatant, total mRNA, and protein lysate were collected to measure the expression of cytokines, chemokines, and transcription factor STAT1. The inflammatory cytokines such as IL-6 and IL-8 has enhance skin inflammation by chemotaxis. There is a big significantly difference with the level of cytokines such as IL-6 and IL-8, and the level of chemokines such as MRC, TARC in between un-transfected and transfected HaCaT cells. Transfected HaCaT cells released low levels cytokines and chemokines where un-transfected HaCaT cells releasing higher levels with cytokines and chemokines. The expression of transcription factor STAT1 which responsible inflammation showed weak in transfected HaCaT cells. According to these results we hypothesized that the increased expression of Per2 gene results enhancing inflammation in HaCaT cells through upregulation of STAT1 expression, which induce skin inflammation in HaCaT cells by releasing cytokines and chemokines. Funding Sources This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government (MSIT) (No. 2022R1F1A1072616). Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)