SIRT1 inhibits releases of HMGB1 and HSP70 from human umbilical vein endothelial cells caused by IL-6 and the serum from a preeclampsia patient and protects the cells from death

Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Yongxiang Yin, Yaling Feng, Hua Zhao, Ziyu Zhao, Hua Yua, Jianjuan Xu, Haisha Che
Preeclampsia (PE), a pregnancy-specific disorder, is associated with inappropriate maternal inflammatory response, oxidative stress, and vascular endothelial cell dysfunction and damage. Releases of high mobility group box-1 (HMGB1) and heat-shock protein 70 (HSP70) into serum are considered to participate in the pathogenesis of PE. The deacetylase, sirtuin 1 (SIRT1), has protective effects against inflammation, apoptosis, and oxidative stress in various pathological conditions. We established a PE mouse model by injection of phosphatidylserine/dioleoyl-phosphatidycholine compounds, followed by measurement of the SIRT1 protein level in the placenta via Western blotting and the serum HMGB1 and HSP70 concentrations via enzyme-linked immunosorbent assay (ELISA). SIRT1 was down-regulated in the placenta of PE mice, in accompany with increased serum HMGB1 and HSP70 concentrations. We incubated human umbilical vein endothelial cells (HUVECs) with IL-6 and the serum from a PE patient individually to mimic status of vein endothelial cells in PE. Western blot and Immunofluorescent assays showed that HMGB1 and HSP70 protein levels were decreased in the cells, but they were increased in the cell medium based on ELISA. These suggested that HMGB1 and HSP70 were forced to be released from the cells. SIRT1 knockdown promoted the releases of HMGB1 and HSP70, whereas its over-expression inhibited the releases. Moreover, SIRT1 protected the cells from death. Collectively, SIRT1 inhibits the releases of HMGB1 and HSP70 from HUVECs caused by IL-6 and the serum from PE patient and protects the cells from death, thus SIRT1 is probably a potentially protective factor in placenta against PE.



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