Inflammation is an essential part for the general or innate immune defenses to defend against tissue damage and accelerate the curing process by providing protection against pathogens. Sulforaphane (SFN) is a natural isothiocyanate that has potential properties against inflammation, along with other protective functions. The purpose of this study was to examine the mechanism of its protective effect on lipopolysaccharide (LPS)-induced inflammation in Raw 264.7 macrophages. Here, we compared LPS-challenged macrophages with or without SFN pretreatment. Macrophages were pre-incubated for 6 h with a wide range of concentrations of SFN (0 to 50 µM), and then treated with LPS for 24 h. Nitric oxide (NO) concentration and gene expression of different inflammatory mediators, i.e., interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, were measured. SFN neither directly reacted with cytokines, nor with NO. To understand the mechanisms, we performed analyses of the expression of regulatory enzyme inducible nitic oxide synthase (iNOS), the transcription factor NF-E2-related factor 2 (Nrf2), and its enzyme heme-oxygenase (HO)-1. Our results revealed that LPS increased significantly the expression of inflammatory cytokines and concentration of NO in non-treated cells. SFN was able to prevent the expression of NO and cytokines through regulating inflammatory enzyme iNOS and activation of Nrf2/HO-1 signal transduction pathway.
Keywords: Nrf2; cytokines; inflammation; lipopolysaccharide; macrophages; sulforaphane.