Dissertation/ Thesis

An AMP kinase activator Energi-704 suppresses inflammatory responses of RAW264.7 induced by lipopolysaccharide

التفاصيل البيبلوغرافية
العنوان: An AMP kinase activator Energi-704 suppresses inflammatory responses of RAW264.7 induced by lipopolysaccharide
Alternate Title: 單磷酸腺苷激酶活化劑Energi-704抑制脂多糖誘發大鼠巨噬細胞RAW264.7發炎反應之分子機制研究
المؤلفون: Chih-Hsuan Chang, 張芷瑄
Thesis Advisors: 高紹軒
سنة النشر: 2013
المجموعة: National Digital Library of Theses and Dissertations in Taiwan
الوصف: 101
Activation of Adenosine monophosphate kinase (AMPK) has been reported to inhibit inflammatory responses induced by lipopolysaccharide (LPS) in vitro and in vivo. An AMPK activator Energi-704 has been demonstrated to ameliorate inflammatory responses of injured skin. However, whether Energi-704 possesses anti-inflammatory activity on activated macrophage, a main player in inflammatory responses, still remain sketchy. Therefore, the present study was aimed to investigate effects of Energi-704 on LPS-stimulated murine macrophage RAW264.7 and the underlying mechanisms.RAW 264.7 cells were used as cell model. After treated with Energi-704 at serial concentrations (0, 0.1, 0.5 and 1 μM) and followed LPS (1 μg/mL), the cells and the cultured medium were separately collected. Expression level of mRNA was analyzed by RT-PCR and real-time quantitative PCR (qPCR). Kinase activation was demonstrated by immunoblot using specific antibodies. Nitric oxide (NO) and reactive oxygen species (ROS) were determined by using Griess reagent and 2’,7’-dichlorofluorescein diacetate (DCFH-DA), respectively. Energi-704 significantly suppressed mRNA levels of pro-inflammatory TNF-α, IL-1β, IL-6, MCP-1, iNOS and COX-2 in RAW264.7 cells stimulated with LPS. In addition, Energi-704 also reduced production of NO and ROS by the stimulated cells. Further investigation showed that Energi-704 reduced activation of PI3K/AKT and mTOR on the activation of AMPK.Our findings show that the Energi-704 robustly inhibited expression of pro-inflammatory components and reduced production of NO and ROS, suggesting Energi-704 possesses potent anti-inflammatory activity against LPS-induced inflammatory responses. Moreover, Energi-704 suppresses LPS-induced inflammatory response by inhibition of phosphatidylinositol 3-kinase/Akt activation and mTOR signaling is possible involved in the anti-inflammatory activity of Energi-704.
Original Identifier: 101CSMU5107038
نوع الوثيقة: 學位論文 ; thesis
وصف الملف: 57
الاتاحة: http://ndltd.ncl.edu.tw/handle/32827441289655311696
رقم الانضمام: edsndl.TW.101CSMU5107038
قاعدة البيانات: Networked Digital Library of Theses & Dissertations