HSPA12B inhibits lipopolysaccharide-induced inflammatory response in human umbilical vein endothelial cells.

Heat shock protein A12B is a newly discovered member of the HSP70 protein family. This study investigated the effects of on lipopolysaccharide (LPS)-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs) and the possible mechanisms involved. A HUVECs inflammatory model was induced by LPS. Overexpression of Hduanyu184212B in HUVECs was achieved by infection with recombinant adenoviruses encoding green fluorescence Knockdown of Hduanyu184212B was achieved by siRNA technique. Twenty four hours after virus infection or siRNA transfection, HUVECs were stimulated with 1 μg/ml LPS for 4 hrs. Endothelial cell permeability ability was determined by transwell permeability assay. The binding rate of human neutrophilic polymorphonuclear leucocytes with HUVECs was examined using myeloperoxidase assay. Cell migrating ability was determined by the wound-healing assay. The mRNA and protein expression levels of interested genes were analyzed by RT-qPCR and Western blot, respectively. The release of cytokines interleukin-6 and tumour necrosis factor-α was measured by ELISA. Hduanyu184212B suppressed LPS-induced HUVEC permeability and reduced adhesion to HUVECs. Hduanyu184212B also inhibited LPS-induced up-regulation of adhesion molecules and inflammatory cytokine expression. By contrast, knockdown of Hduanyu184212B enhanced LPS-induced increases in the expression of adhesion molecules and inflammatory cytokines. Moreover, Hduanyu184212B activated PI3K/Akt signalling pathway and pharmacological inhibition of this pathway by Wortmannin completely abrogated the protection of Hduanyu184212B against inflammatory response in HUVECs. Our results suggest that Hduanyu184212B attenuates LPS-induced inflammatory responses in HUVECs via activation of PI3K/Akt signalling pathway.

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