Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages - PubMed (original) (raw)

. 2014 Jan 3;443(1):326-32.

doi: 10.1016/j.bbrc.2013.11.122. Epub 2013 Dec 7.

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

Dan Chen et al. Biochem Biophys Res Commun. 2014.

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.

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.

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