Original Article Diosgenin suppressed LPS-induced inflammation through inhibiting HSP90 induced phosphorylation of NF-κb p65

Xianqian Li, Ning Wu, Ronghuan Yu, Chao Guan, Ting Xu, Jiaxi Wu
2018 Int J Clin Exp Med   unpublished
Asthma is a heterogeneous disease which affects millions of people's life. Glucocorticoids (GCs) are able to relieve their symptoms through interacting with glucocorticoid receptors (GRs). Diosgenin, extracted from Dioscorea nipponica, was hypothesized to exert anti-inflammation effect through interaction with GRs as well. In this study, lipopolysaccharide (LPS)-inducted primary human bronchial epithelial cells (HBECs) were utilized as asthma models. ELISA was applied to measure the secretion
more » ... ure the secretion of IL-1β and IL-6. Quantative PCR was applied to evaluate the expression of IL-1β, IL-6 and GRα. Western blot was utilized to test the protein level of HSP90 and GRα and phosphorylation of NF-κb p65. As a result, our ELISA and quantative PCR data demonstrated that diosgenin and prednisone acetate suppressed the secretion of IL-1β and IL-6 as well as their mRNA level. Our western blot data indicated that both diosgenin and prednisone acetate treatment enhanced the expression of GRα and inhibited the phosphorylation of NF-κb p65 without affecting the protein level of HSP90. After applied HSP90 inhibitor (17-AAG) to cells, we found that the secretion of IL-1β and IL-6 and the phosphorylation of NF-κb p65 were both suppressed. As a conclusion, prednisone acetate treatment and diosgenin treatment might suppress inflammation by inhibiting HSP90 induced phosphorylation of NF-κb p65 together with GR activation. These data revealed novel molecular mechanism of the suppression of diosgenin on inflammation.
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