文献类型：期刊文献

英文题名：Geranylgeranylacetone Ameliorates Skin Inflammation by Regulating and Inducing Thioredoxin via the Thioredoxin Redox System

作者：Jin, Tiancheng[1];You, Yitong[1];Fan, Wenjie[1];Wang, Junyang[1];Chen, Yuhao[1];Li, Shujing[1];Hong, Siyuan[1];Wang, Yaxuan[1];Cao, Ruijie[1];Yodoi, Junji[2];Tian, Hai[1,3]

机构：[1]Shaoxing Univ, Coll Med, Dept Basic Med, Shaoxing 312000, Peoples R China;[2]Kyoto Univ, Inst Virus Res, Dept Biol Response, Lab Infect & Prevent, Kyoto 6068507, Japan;[3]Jiaozhimei Biotechnol Shaoxing Co Ltd, Shaoxing 312000, Peoples R China

年份：2023

卷号：12

期号：9

外文期刊名：ANTIOXIDANTS

收录：SCI-EXPANDED(收录号：WOS:001075883600001)、、Scopus(收录号：2-s2.0-85172266974)、WOS

基金：The authors deeply appreciate Akira Yamauchi and Atsushi Fukunaga for pointed advice and discussion for writing this article. The contribution of Jiedong Zhou and Cuixue Wang to the revision of the text is also gratefully acknowledged.

语种：英文

外文关键词：geranylgeranylacetone; irritant contact dermatitis; thioredoxin redox system; PI3K/Akt/Nrf2 signaling pathway; anti-inflammatory effect and mechanism

外文摘要：Geranylgeranylacetone (GGA) exerts cytoprotective activity against various toxic stressors via the thioredoxin (TRX) redox system; however, its effect on skin inflammation and molecular mechanism on inducing the TRX of GGA is still unknown. We investigated the effects of GGA in a murine irritant contact dermatitis (ICD) model induced by croton oil. Both a topical application and oral administration of GGA induced TRX production and Nrf2 activation. GGA ameliorated ear swelling, neutrophil infiltration, and inhibited the expression of TNF-alpha, IL-1 beta, GM-CSF, and 8-OHdG. GGA's cytoprotective effect was stronger orally than topically in mice. In vitro studies also showed that GGA suppressed the expression of NLRP3, TNF-alpha, IL-1 beta, and GM-CSF and scavenged ROS in PAM212 cells after phorbol myristate acetate stimulation. Moreover, GGA induced endogenous TRX production and Nrf2 nuclear translocation in PAM212 cells (dependent on the presence of ROS) and activated the PI3K-Akt signaling pathway. GGA significantly downregulated thioredoxin-interacting protein (TXNIP) levels in PAM212 cells treated with or without Nrf2 siRNA. After knocking down Nrf2 in PAM212 cells, the effect of GGA on TRX induction was significantly inhibited. This suggests that GGA suppress ICD by inducing endogenous TRX, which may be regulated by PI3K/Akt/Nrf2 mediation of the TRX redox system.