EMAIL THIS PAGE TO A FRIEND

Experimental cell research

Angiotensin II-induced hypertensive renal inflammation is mediated through HMGB1-TLR4 signaling in rat tubulo-epithelial cells.


PMID 26033363

Abstract

Angiotensin II is a vaso-constrictive peptide that regulates blood pressure homeostasis. Even though the inflammatory effects of AngII in renal pathophysiology have been studied, there still exists a paucity of data with regard to the mechanism of action of AngII-mediated kidney injury. The objective of this study was to elucidate the mechanistic role of HMGB1-TLR4 signaling in AngII-induced inflammation in the kidney. Rat tubular epithelial cells (NRK52E) were treated with AngII over a preset time-course. In another set of experiments, HMGB1 was neutralized and TLR4 was knocked down using small interfering RNA targeting TLR4. Cell extracts were subjected to RT-PCR, immunoblotting, flow cytometry, and ELISA. AngII-induced inflammation in NRK52E cells increased gene and protein expression of TLR4, HMGB1 and key proinflammatory cytokines (TNFα and IL1β). Pretreatment with Losartan (an AT1 receptor blocker) attenuated the AngII-induced expression of TLR4 and inflammatory cytokines. TLR4 silencing was used to elucidate the specific role played by TLR4 in AngII-induced inflammation. TLR4siRNA treatment in these cells significantly decreased the AngII-induced inflammatory effect. Consistent observations were made when the Ang II treated cells were pretreated with anti-HMGB1. Downstream activation of NFκB and rate of generation of ROS was also decreased on gene silencing of TLR4 and exposure to anti-HMGB1. These results indicate a key role for HMGB1-TLR4 signaling in AngII-mediated inflammation in the renal epithelial cells. Our data also reveal that AngII-induced effects could be alleviated by HMGB1-TLR4 inhibition, suggesting this pathway as a potential therapeutic target for hypertensive renal dysfunctions.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

EHU086621 MISSION® esiRNA, esiRNA human TLR4 (esiRNA1)