| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所 === 99 === Abstract
Despite the advance of medical research, sepsis still have a high mortality in intensive care unit. Sepsis is a systemic inflammatory response to infections. Lipopolysaccharide (LPS or endotoxin), plays the key role important in inducing sepsis. Immune cells , like macrophages, would release inflammation-associated cytokines ( such as TNF-α、IFN-γ、IL-1、IL-6 ), nitric oxide(NO) and prostaglandin E2 (PGE2.) Macrophages play an important role in innate immune system. Several studies have indicated that macrophage would produce a mounts of NO by triggering NOS2 gene expression when inducing by LPS.
Pheophytin b is one component of green tea, which shows anti-inflammation effects.Our study investigated that the immune modulation and its molecular mechanisms of pheophytin b repressing NO and PGE2 produced by LPS-treated macrophages (RAW264.7 cells, a murine macrophage cell lines). Using cytotoxic assay, pheophytin b showed low toxicity on macrophages and it reduced LPS-induced NO and PGE2 production. We found pheophytin b not only reduced the NOS2 mRNA and protein expression but also reduced COX-2 mRNA and protein expression. However, it did not effect the MAPK pathway, including p38, ERK, and JNK pathway. About NF-κB pathway, pheophytin b did not repress the phosporylation of IκB-αand translocation of phospo-P65 into nucleus. Even though transcription factor,AP-1,have not been impacted. But pheophytin b inhibited STAT1 and Akt activation.
In summary, the suppression of NOS2 and COX-2 expression by pheophytin b may be through STAT-1/PI3K/Akt pathway
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