Sulforaphane activates a protective Nrf2 response and reduces inflammatory markers in microglia cells

Abstract

Cells exposed to oxidative stress require intrinsic mechanisms to abrogate harmful effects of un‐neutralized reactive oxygen species. Nrf2 is a primary transcription factor involved in detoxification. Induction of antioxidant response element (ARE) genes heme oxygenase (HO1), glutathione‐S‐transferase (GSTA), and NAD(P)H quinine oxidoreductase (NQO1) is directly mediated through Nrf2 activation. While Nrf2 has been broadly studied, data characterizing its role in the central nervous system, particularly in microglia, is limited. In this study, BV2 cells were treated with sulforaphane (SFN) to test its effect on activation of Nrf2. SFN treatment increased mRNA expression of HO1, GSTA, and NQO1. In order to determine if the protective effects of Nrf2 activation could reverse inflammatory characteristics of toxin‐activated microglia, BV2 cells were treated with LPS. Cells responded to LPS with significantly increased expression of inflammatory genes. Pre‐treatment with SFN upregulated ARE genes while down‐regulating the increase in inflammatory cytokines IL‐6, IL‐1β, TNFα, and iNOS caused by LPS. Additionally, SFN negated increased nitric oxide production induced by LPS. Changes in the Nrf2 signaling pathway in microglia may be implicated in cognitive decline associated with an aging inflammatory state. This work paves the way for future studies in vivo. 538 NIH 2 R01AG016710C