Abstract
Besides stimulating vasoconstriction, Angiotensin II is also well known in inducing reactive oxygen species and promoting inflammatory phenotype switch via its type 1 receptor. In clinic, Angiotensin II type 1 (AT1) receptor blocker like candesartan has been widely applied as an antihypertensive medication. We previous have demonstrated that a higher dose of candesartan plays a protective role after kidney injury. However, whether candesartan could exhibit anti-inflammatory effects remains unclear. Here, by stimulating isolated human embryonic kidney epithelial cells with tumor necrosis factor-α (TNF-α), we observed the anti-inflammation capacity of candesartan ex vivo. It was found that pre-treat with candesartan significantly suppressed transforming growth factor-β (TGF-β) and interleukin-6 (IL-6) expression after incubation with TNF-α. Surprisingly, silence of angiotensin II type 1 receptor has little effects on reducing TGF-β or IL-6 products. Furthermore, candesartan inhibited TNF-α-induced oxidative stress in the primary cultured tubular epithelial cells. Overall, our data indicates that candesartan suppresses TNF-α-induced inflammatory cytokine production by inhibiting oxidative stress, rather than block AT1 receptor activity.
Highlights
As the key peptide of renin–angiotensin system (RAS), Angiotensin II (AngII), plays a central role in regulating blood pressure, and maintainingIt is suggested that renal inflammation contributes to renal disease progression (AndersBIOMEDICAL SCIENCESAn Acad Bras Cienc (2019) 91(2)CANDESARTAN INHIBITS INFLAMMATION BY AngII type 1 receptor (AT1R) INDEPENDENT WAY et al 2018)
In our previous in vivo study in the model of chronic renal damage of spontaneous hypertensive rat, we found that candesartan was able to suppress NF-κB activation, tubular chemokines expression, renal inflammation and injury, even if AT1R had already been blocked completely (Yu et al 2007), suggesting that AT1R-independent mechanisms may be involved in
To further examine the role of AT1R in the antiinflammatory effects of candesartan, the siRNA method was used to knock down AT1R in Human embryonic kidney epithelial cells (HKC)
Summary
As the key peptide of renin–angiotensin system (RAS), Angiotensin II (AngII), plays a central role in regulating blood pressure, and maintainingIt is suggested that renal inflammation contributes to renal disease progression (AndersBIOMEDICAL SCIENCESAn Acad Bras Cienc (2019) 91(2)CANDESARTAN INHIBITS INFLAMMATION BY AT1R INDEPENDENT WAY et al 2018). As the key peptide of renin–angiotensin system (RAS), Angiotensin II (AngII), plays a central role in regulating blood pressure, and maintaining. It is suggested that renal inflammation contributes to renal disease progression Angiotensin II play key role in inducing reactive oxygen species and promoting inflammatory phenotype switch via its type 1 receptor (Ren et al 2017, Sifi et al 2017). In our previous in vivo study in the model of chronic renal damage of spontaneous hypertensive rat, we found that candesartan was able to suppress NF-κB activation, tubular chemokines expression, renal inflammation and injury, even if AT1R had already been blocked completely (Yu et al 2007), suggesting that AT1R-independent mechanisms may be involved in. The present study was designed to determine the AT1Rindependent mechanism of candesartan on its anti-inflammatory effects
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