Inhibitory Effect of 3-(4-Hydroxyphenyl)-1-(thiophen-2-yl) prop-2-en-1-one, a Chalcone Derivative on MCP-1 Expression in Macrophages via Inhibition of ROS and Akt Signaling.
10.4062/biomolther.2014.127
- Author:
Mi Jin KIM
1
;
Taraman KADAYAT
;
Yeon Ji UM
;
Tae Cheon JEONG
;
Eung Seok LEE
;
Pil Hoon PARK
Author Information
1. College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. tcjeong@yu.ac.kr, eslee@yu.ac.kr, parkp@yu.ac.kr
- Publication Type:Original Article
- Keywords:
Chalcone;
MCP-1;
Reactive oxygen species;
Inflammation;
Lipopolysaccharide
- MeSH:
Cell Survival;
Chalcone*;
Chalcones;
Chemokine CCL2;
Chemokines;
Gene Expression;
Inflammation;
Luciferases;
Macrophages*;
Phosphorylation;
Reactive Oxygen Species;
RNA, Messenger;
Transcription Factor AP-1;
Transcriptional Activation
- From:Biomolecules & Therapeutics
2015;23(2):119-127
- CountryRepublic of Korea
- Language:English
-
Abstract:
Chalcones (1,3-diaryl-2-propen-1-ones), a subfamily of flavonoid, are widely known to possess potent anti-inflammatory and anti-oxidant properties. In this study, we investigated the effect of 3-(4-Hydroxyphenyl)-1-(thio3-(4-Hydroxyphenyl phen-2-yl)prop-2-en-1-one (TI-I-175), a synthetic chalcone derivative, on endotoxin-induced expression of monocyte chemoattractant protein-1 (MCP-1), one of the key chemokines that regulates migration and infiltration of immune cells, and its potential mechanisms. TI-I-175 potently inhibited MCP-1 mRNA expression stimulated by lipopolysaccharide (LPS) in RAW 264.7 macrophages without significant effect on cell viability. Treatment of cells with TI-I-175 markedly prevented LPS-induced transcriptional activation of activator protein-1 (AP-1) as measured by luciferase reporter assay, while nuclear factor-kappaB (NF-kappaB) activity was not inhibited by TI-I-175, implying that TI-I-175 suppressed MCP-1 expression probably via regulation of AP-1. In addition, TI-I-175 treatment significantly inhibited LPS-induced Akt phosphorylation and led to a significant decrease in reactive oxygen species (ROS) production by LPS, which act as up-stream signaling events required for AP-1 activation in RAW 264.7 macrophages. Taken together, these results indicate that TI-I-175 suppresses MCP-1 gene expression in LPS-stimulated RAW 264.7 macrophages via suppression of ROS production and Akt activation.
