Regulation of NF-κB activation by PPARγ in mice with meningoencephalitis caused by Angiostrongylus cantonensis

• Main Authors: Chi-Yang, 彭啟揚
• Other Authors: 賴世展
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/33328466910858852838

碩士 === 中山醫學大學 === 醫學研究所 === 99 === Peroxisome-proliferator activator receptor gamma (PPARγ) is a member of the nuclear receptor family of ligand-dependent transcription factors that regulate glucose homeostasis, lipid and lipoprotein metabolism, inflammatory genes, and consequently a key role in CNS disorders. Previous studies revealed that activated PPARγ functioned as an anti-inflammatory role which inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and regulates the expressions of inflammatory proteins, whereas its role in parasitic meningoencephalitis is still unknown. In this study, we investigated the role of PPARγ and related mechanisms in eosinophilic meningoencephalitis caused by A. cantonensis. By using GW9662, the specific antagonist of PPARγ, in animal model of angiostrongyliasis, we observed decreased proteins expression of IκB-α and increased proteins expression of phospho-IκB-α, phospho-NF-κB in mice brain. Then we investigated NF-κB related downstream proteins such as COX-2, NOSs, IL-1β by Western blot or Enzyme-linked immunosorbent assay (ELISA), and the proteins expression were upregulated. The results of gelatin zymography showed that the activities of MMP-9 were upregulated also. These results suggest that PPARγ, in angiostrongyliasis, may acts anti-inflammation role in many NF-κB related categories, including NOS related oxidative stress, cytokines, prostanoids, and MMPs cascade through increasing IκB-α protein levels.