Sirtuin 1 (Sirt1) Overexpression in BaF3 Cells Contributes to Cell Proliferation Promotion, Apoptosis Resistance and Pro-Inflammatory Cytokine Production

Abstract

BackgroundB lymphocyte hyperactivity is a main characteristic of systemic lupus erythematosus (SLE), and B lymphocytes play a prominent pathogenic role in the development and progression of SLE. The aim of this study was to investigate the role of Sirtuin 1 (Sirt1) in B lymphocytes.Material/MethodsMouse B lymphocytes BaF3 was transfected with Sirt1 vector or shRNA against Sirt1. Then the transfected cells viability and apoptosis were respectively determined by MTT assay and flow cytometry. In addition, the mRNA levels of three pro-inflammatory cytokines and p53 were detected by RT-PCR. Furthermore, the expression levels of nuclear factor-kappa B (NF-κB) pathway proteins were measured by Western blot.ResultsOverexpression of Sirt1 significantly increased cell proliferation (p<0.05 or p<0.01) and significantly suppressed apoptosis (p<0.05). The mRNA level expressions of interleukin 1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) were significantly upregulated (p<0.05 or p<0.01), whereas p53 was significantly downregulated (p<0.05) by Sirt1 overexpression. In addition, the inhibitory subunit of NF-κB (IκBα) and p65 were significantly activated and phosphorylated (p<0.01 or p<0.001), and B-Cell CLL/Lymphoma 3 (Bcl-3) was significantly upregulated (p<0.05) by Sirt1 overexpression.ConclusionsThese results suggested that Sirt1 overexpression could promote BaF3 cell proliferation, inhibit apoptosis, and upregulate pro-inflammatory cytokines. The NF-κB pathway might be involved in these effects of Sirt1 on BaF3 cells, and Sirt1 might be a potential risk factor of SLE.

T and B Cell Metabolism in Older Adults

“…It also serves a negative regulator of Th1, Th2 and Treg cell activation but seems to improve CD8 + T cell functions by enhancing transcription of T-bet [265]. Little is known about the effect of SIRTs on B cells but SIRT1 seems to increase B cell survival [266]. Resveratrol, an activator of Sirt1 is under scrutiny as potential immune modulator and may prove to be useful as an agent to combat autoimmune diseases and inflammaging [265].…”

HIF1α Deficiency in Dendritic Cells Attenuates Symptoms and Inflammatory Indicators of Allergic Rhinitis in a SIRT1-Dependent Manner

“…SIRT1 is one kind of histone deacetylase that is essential for regulating inflammatory cytokine production and modulating naïve CD4 + T cell differentiation [17, 25, 26], which suggests a potential role of SIRT1 in allergic rhinitis development. In an OVA-induced allergic rhinitis mouse model, SIRT1 expression levels significantly decreased.…”

Regulation of Adaptive Immune Cells by Sirtuins

“…Thus far, the limited literature on sirtuin activity in B cells indicates sirtuins support B cell viability, proliferation, and function. SIRT1 overexpression by viral transfection in BaF3 B cells (a murine B cell line) has been shown to support enhanced viability (mediated in part by a decrease in p53) and increased cytokine production (68). A short, non-coding microRNA, miR-132, is increased in B cells of patients with multiple sclerosis (MS) concurrent with a reduced expression of SIRT1 (69).…”