Modulator Effect of AT1 Receptor Knockdown on THP-1 Macrophage Proinflammatory Activity

Currently, it is known that angiotensin II (AngII) induces inflammation, and an AT₁R blockade has anti-inflammatory effects. The use of an AT₁ receptor antagonist promotes the inhibition of the secretion of multiple proinflammatory cytokines in macrophages, as well as a decrease in the concentration of reactive oxygen species. The aim of this study was to determine the effect of AT₁ receptor gene silencing on the modulation of cytokines (e.g., IL-1β, TNF-α, and IL-10) in THP-1 macrophages and the relation to the gene expression of NF-κB.

We evaluated the gene expression of PPAR-γ in THP-1 macrophages using PMA (60 ng/mL). For the silencing, cells were incubated with the siRNA for 72 h and telmisartan (10 µM) was added to the medium for 24 h. After that, cells were incubated during 1 and 24 h, respectively, with Ang II (1 µM). The gene expression levels of AT₁R, NF-κB, and cytokines (IL-1β, TNF-α, and IL-10) were measured by RT-qPCR.

We observed that silencing of the AT₁ receptor causes a decrease in the expression of mRNA of proinflammatory cytokines (IL-1β and TNF-α), NF-κB, and PPAR-γ.

We conclude that AT₁R gene silencing is an alternative to modulating the production of proinflammatory cytokines such as TNF-α and IL-1β via NF-κB in macrophages and having high blood pressure decrease.