| Summary: | 碩士 === 國立成功大學 === 生物醫學工程學系 === 106 === Sepsis is a systemic inflammatory response caused by bacteria infection. It is known that star-shaped structure polypeptides efficiently interact with the outer membranes of bacteria and enhance antimicrobial activity. However, there were few studies reported their ability on LPS-induced sepsis. For this, linear and star polypeptides were synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs) with benzoic acid modified as functional group. In this study, these synthetic polypeptides show highly affinity to the endotoxin LPS by electrostatic force and may reduce the toxicity of LPS through forming a compounded aggregation. Furthermore, we found that star polypeptide with modification inhibited the expression of pro-inflammatory mediators and cytokines such as inflammatory nitric oxide, TNF-α and IL-6 from the LPS-stimulated RAW264.7 macrophages and exhibited significant anti-inflammatory properties as well compared to linear modified polypeptide and non-modified star polypeptide. Mechanism studies revealed that the inhibitory effects of modified star polypeptide was mainly mediated by the inhibition of phosphorylated PI3K/Akt pathway, partial MAPK pathway and the down-regulated nuclear translocation of p65 expression which is the main transcription factor to regulate the inflammation. Furthermore, modified star polypeptide decreased the production of TNF-α, IL-6 in the LPS-induced sepsis mice model without causing tissue damage. These results support that this simply synthesized star polypeptide with additional functionality is a promising therapeutic agent for bacteria induced diseases.
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