Quercetin and HSC70 coregulate the anti-inflammatory action of the ubiquitin-like protein MNSFβ.

Abstract

Quercetin is a flavonol that modifies many cellular processes. Monoclonal nonspecific suppressor factor β is a member of the ubiquitin-like family of proteins that are involved in various biological processes. It has been demonstrated that quercetin regulates the effect of MNSFβ on tumor necrosis factor-α secretion in lipopolysaccharide (LPS)-stimulated macrophages. This study found that quercetin and the heat shock protein HSC70 coregulate the action of MNSFβ. Quercetin dose-dependently suppressed the LPS/interferon γ-induced nitric oxide production without cytotoxicity in the macrophage-like cell line Raw264.7. SiRNA knockdown experiments showed that quercetin inhibited the MNSFβ and HSC70 siRNA-mediated enhancement of TNFα and the production of RANTES, a member of C-C chemokine superfamily, in LPS-stimulated Raw264.7 cells. Western blot analysis showed that quercetin and HSC70 regulated ERK1/2 activation and LPS-stimulated IκBα degradation by affecting the complex formation of MNSFβ and the proapoptotic protein Bcl-G. Moreover, MNSFβ is implicated in TLR4/MyD88 signaling but not in TLR3 signaling. HSC70 is an important chaperone that facilitates the stabilization of MNSFβ. Quercetin may negatively control the function of MNSFβ by regulating the action of the molecular chaperone HSC70. MNSFβ mediates TLR4/Myd88 signaling but not TLR3 signaling.