Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages

详细信息    查看全文

• 作者：Dan Chen ; Aijing Bi ; Xiaoliang Dong ; Yi Jiang ; Bing Rui ; Jinjiao Liu ; Zhimin Yin ; Lan Luo
• 关键词：HMGB1 ; high mobility group B-1 ; RAGE ; receptor for advanced glycation end products
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：3 January, 2014
• 年：2014
• 卷：443
• 期：1
• 页码：326-332
• 全文大小：2190 K

文摘

Septic diseases represent the prevalent complications in intensive care units. Luteolin, a plant flavonoid, has potent anti-inflammatory properties; however, the molecular mechanism beneath luteolin mediated immune modulation remains unclear. Here in vitro investigations showed that luteolin dose-dependently inhibited LPS-triggered secretion and relocation of high mobility group B-1 (HMGB1) and LPS-induced production of tumor necrosis factor alpha (TNF-伪) and nitric oxide (NO) in macrophages. The mechanism analysis demonstrated that luteolin reduced the release of HMGB1 through destabilizing c-Jun and suppressed HMGB1-induced aggravation of inflammatory cascade through reducing Akt protein level. As an inhibitor of Hsp90, luteolin destabilized Hsp90 client protein c-Jun and Akt. In vivo investigations showed that luteolin effectively protected mice from lipopolysaccharide (LPS)-induced lethality. In conclusion, the present study suggested that luteolin may act as a potential therapeutic reagent for treating septic diseases.