SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway

Chronic inflammation induced by amyloid-beta (A beta) plays a key role in the development of age-related macular degeneration (AMD), and matrix metalloproteinase-9 (MMP-9), interleukin (IL)-6, and IL-8 may be associated with chronic inflammation in AMD. Sirtuin 1 (SIRT1) regulates inflammation via inhibition of nuclear factor-kappa B (NF-kappa B) signaling, and resveratrol has been reported to prevent A beta-induced retinal degeneration; therefore, we investigated whether this action was mediated via activation of SIRT1 signaling. Human adult retinal pigment epithelial (RPE) cells were exposed to A beta, and overactivation and knockdown of SIRT1 were performed to investigate whether SIRT1 is required for abrogating A beta-induced inflammation. We found that A beta-induced RPE barrier disruption and expression of IL-6, IL-8, and MMP-9 were abrogated by the SIRT1 activator SRT1720, whereas alterations induced by A beta in SIRT1-silenced RPE cells were not attenuated by SRT1720. In addition, SRT1720 inhibited A beta-mediated NF-kappa B activation and decrease of the NF-kappa B inhibitor, I kappa B alpha. Our findings suggest a protective role for SIRT1 signaling in A beta-dependent retinal degeneration and inflammation in AMD.