Sirtuin-1 is involved in lipopolysaccharide- and interferon beta-mediated interleukin-10 regulation in human monocytes

Sirtuin-1 (SIRT1) is a histone deacetylase involved in various biological processes, including aging, neuroprotection, lipid metabolism, and T cell tolerance. We previously showed that SIRT1 regulates human B cell cytokine production and is downregulated in the B cells of multiple sclerosis (MS) patients, leading to aberrant cytokine profile. Here, we investigated the role of SIRT1 in interleukin (IL)-10 regulation of human peripheral blood monocytes. The expression of SIRT1 mRNA in monocytes was suppressed by treatment with lipopolysaccharide (LPS), but enhanced by interferon (IFN) beta. Although no differences were observed in SIRT1 expression in monocytes from untreated MS patients and healthy controls, higher SIRT1 expression was detected in monocytes from IFN beta-treated MS patients compared to those from untreated patients. Introduction of resveratrol, an SIRT1 activator, enhanced LPS-induced IL-10 production from monocytes in vitro. IFN beta similarly enhanced IL-10 production from monocytes, but this enhancement was weakened by treatment with EX527, an SIRT1 inhibitor. Taken together, these observations suggest that SIRT1 is involved in IL-10 regulation in human monocytes and that the induction of IL-10 by IFN beta is modulated by SIRT1. Due to its regulatory effects on immune cells, in addition to its neuroprotective activity, SIRT1 is an attractive therapeutic target in MS.