Biomol Ther.  2015 Mar;23(2):119-127. 10.4062/biomolther.2014.127.

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

• Kim MJ
• Kadayat T
• Um YJ
• Jeong TC
• Lee ES
• Park PH

• KMID: 2380344
• DOI: http://doi.org/10.4062/biomolther.2014.127

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.

Keyword

Chalcone; MCP-1; Reactive oxygen species; Inflammation; Lipopolysaccharide

MeSH Terms

Cell Survival
Chalcone*
Chalcones
Chemokine CCL2
Chemokines
Gene Expression
Inflammation
Luciferases
Macrophages*
Phosphorylation
Reactive Oxygen Species
RNA, Messenger
Transcription Factor AP-1
Transcriptional Activation
Chalcone
Chalcones
Chemokine CCL2
Chemokines
Luciferases
RNA, Messenger
Reactive Oxygen Species
Transcription Factor AP-1