Dihydroaustrasulfone alcohol抑制LPS誘導巨噬細胞發炎反應

Inhibitory effect of dihydroaustrasulfone alcohol on LPS-induced inflammatory response in macrophages

劉秀君(Shu-Juen Liu)

指導教授 ： 王惠君

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2016年)

摘要

發炎過程與許多慢性疾病具有關聯性，例如心血管疾病與癌症。因此研發小分子藥物來控制發炎不只可減緩發炎的過程，也有助於延緩慢性疾病的病程甚或是幫助避免其發生。本篇研究所使用的藥物dihydroaustrasulfone alcohol (H10) 是由福爾摩沙瘤軟珊瑚Cladiella australis中分離而得，並且已於先前文獻中發現其具有抑制革蘭氏陰性菌內毒素(lipopolysaccharide; LPS) 所誘發的iNOS蛋白質表現。因此我們使用H10在LPS誘導發炎反應的小鼠巨噬細胞RAW 264.7中來探討其抑制發炎之效果與可能的機轉。研究結果顯示H10可抑制LPS引起的nitric oxide (NO)與prostaglandin E2 (PGE2) 的產生，且其關鍵合成酶方面，iNOS蛋白表現量同樣被抑制，但對COX-2蛋白質的表現量則影響有限。我們發現H10可抑制NFκB, ERK, 以及Akt的活化，但p38與JNK則不受影響，這或許跟H10下調節iNOS基因的表現有關。此外cytokine array assay結果顯示H10可抑制LPS在巨噬細胞中所引起的一些cytokines與chemokines產生。這些結果顯示H10展現了抑制發炎反應之效果，並且研究其分子作用機制可幫助運用於治療發炎相關的疾病。

關鍵字

dihydroaustrasulfone alcohol ； 巨噬細胞 ； RAW 264.7 ； 發炎

並列摘要

Inflammation processes have been linked to various chronic diseases including cardiovascular diseases and cancers. Discovery small molecules in controlling inflammation can not only prevent aggravate inflammatory processes but also have opportunities to control other chronic diseases. The compound dihydroaustrasulfone alcohol (H10) was isolated from the Formosan soft coral Cladiella australis and shown to inhibit lipopolysaccharide (LPS)-induced iNOS protein expression. Here, we investigate the signaling mechanisms involved in H10 effects on the LPS-induced inflammatory response in RAW 264.7 macrophages. Our results showed H10 attenuates LPS-induced NO and prostaglandin E2 production. Examined for their catalytic enzymes showed a decreased iNOS but not Cox-2 protein expression. We found phosphorylation activation of NFκB, ERK, and Akt, but not p38 and JNK, inhibited by H10 might involve in down-regulation of gene expression. Besides, the cytokine array assay showed H10 also attenuated several cytokines and chemokines secretion in LPS-stimulated macrophages, indicating H10 have potential against inflammation. Research on molecular mechanisms of H10 in advance is necessary for its application in treating diseases associated with inflammation.

並列關鍵字

dihydroaustrasulfone alcohol ； macrophages ； RAW 264.7 ； inflammation

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