Title: Pheophytin a Inhibits Inflammation via Suppression of LPS-Induced Nitric Oxide Synthase-2, Prostaglandin E2, and Interleukin-1 beta of Macrophages
Authors: Lin, Chun-Yu
Lee, Chien-Hsing
Chang, Yu-Wei
Wang, Hui-Min
Chen, Chung-Yi
Chen, Yen-Hsu
Institute of Biomedical Engineering
Keywords: pheophytin a;NO;signal transducers and activators of transcription 1 (STAT-1);anti-inflammation
Issue Date: 1-Dec-2014
Abstract: Inflammation is a serious health issue worldwide that induces many diseases such as sepsis. There has been a vast search for potentially effective drugs to decrease mortality from sepsis. Pheophytin a is a chlorophyll-related compound derived from green tea. We found that pre-treatment with pheophytin a suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-1 beta in RAW 264.7 macrophages. NO synthase-2 (NOS2) and cyclooxygenase-2 (COX-2) expression levels were repressed by pre-treatment with pheophytin a at both the transcriptional and translational levels. Pheophytin a inhibited NOS2 promoter activity, but not its mRNA stability, through extracellular signal-regulated kinase (ERK1/2). This suppression was reversed by ERK1/2 inhibitor (U0126). Pheophytin a reduced signal transducers and activators of transcription 1 (STAT-1) activation, without an obvious influence on activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappa B). These results suggest that pheophytin a functions by down-regulating the transcriptional levels of inflammatory mediators and blocking the ERK and STAT-1 pathways.
URI: http://dx.doi.org/10.3390/ijms151222819
ISSN: 1422-0067
DOI: 10.3390/ijms151222819
Volume: 15
Issue: 12
Begin Page: 22819
End Page: 22834
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