The anti-inflammatory effects of sulforaphane are not mediated by the Nrf2 pathway

Sulforaphane (SFN) is a naturally occurring compound, found in cruciferous vegetables. SFN is a potent activator of the endogenous anti-oxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Due to its anti-oxidant and anti-inflammatory properties SFN has been identified as a potential treatment for a number of diseases including chronic obstructive pulmonary (COPD). We confirmed that SFN activates of the Nrf2 pathway and induces the expression of haemoxygenase (HO)-1 and NAD(P)H:Quinone Oxireductase (NQO)-1. SFN suppressed interleukin (IL)-1b-induced and IL-1b plus oxidative stress (hydrogen peroxide, H 2 O 2 )-induced CXCL8 expression in a concentration-dependent manner in human bronchial epithelial and monocyte cell lines. Nrf2 siRNA significantly reduced the ability of SFN to enhance Nrf2-mediated induction of HO-1 and NQO-1 without any effect on the ability of SFN to suppress IL-1b- and IL-1b+H 2 O 2 -induced CXCL8 expression in these cells. Our results suggest that the anti-inflammatory effects of SFN occur independently of Nrf2 in human airway epithelial cells and macrophages. Figure legend. Nrf2 knockdown using siRNA abrogates the ability of sulpforophane to induce Nrf2 activation (A & B) and that of the downstream target NQO-1 (c & d) in BEAS-2B cells. Nrf2 knockdown does not have a significant effect on the ability of sulforophane to suppress IL-1b-induced CXCL8 release in BEAS-2B or U937 cells (e & f).