硫氧还蛋白
化学
TXNIP公司
PI3K/AKT/mTOR通路
炎症
细胞生物学
内生
蛋白激酶B
奥兰诺芬
药理学
硫氧还蛋白还原酶
信号转导
氧化应激
生物化学
生物
免疫学
类风湿性关节炎
作者
Tianlin Jin,Yiran You,Wenhui Fan,Jun-Yang Wang,Yuhao Chen,Shujing Li,Sung‐Hoo Hong,Yaxuan Wang,Ruijie Cao,Junji Yodoi,Hai Tian
出处
期刊:Antioxidants
[MDPI AG]
日期:2023-08-31
卷期号:12 (9): 1701-1701
被引量:1
标识
DOI:10.3390/antiox12091701
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-α, IL-1β, 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-α, IL-1β, 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.
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