title: Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages.
abstract: 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-α) 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.
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, China.
authors: Dan
authors: D
authors: Chen
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, China.
authors: Aijing
authors: A
authors: Bi
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, China.
authors: Xiaoliang
authors: X
authors: Dong
authors: Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210046, China.
authors: Yi
authors: Y
authors: Jiang
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, China.
authors: Bing
authors: B
authors: Rui
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, China.
authors: Jinjiao
authors: J
authors: Liu
authors: Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210046, China. Electronic address: yinzhimin@njnu.edu.cn.
authors: Zhimin
authors: Z
authors: Yin
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, China. Electronic address: lanluo@nju.edu.cn.
authors: Lan
authors: L
authors: Luo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D004195:Disease Models, Animal; D057809:HEK293 Cells; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D047311:Luteolin / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018841:HSP90 Heat-Shock Proteins; D008070:Lipopolysaccharides; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D047311:Luteolin
keywords: HMGB1; Heat shock protein 90; High mobility group B-1; Lipopolysaccharide; Luteolin; Macrophage; RAGE; c-Jun; high mobility group B-1; receptor for advanced glycation end products