Sulfavant A: a novel modulator of microglia activity

Chronic activated microglia is correlated with neuronal cell death in several neurodegenerative diseases. Activated microglia has been classified in two states, classic (M1) and alternative (M2), considered a pro-inflammatory and an anti-inflammatory state, respectively. Thus, functional modulation of microglial phenotypes has been deemed as a potential therapeutic strategy. Recently, a novel non-natural chimeric sulfoglycolipid, named Sulfavant A (?-SQDG), has shown promising immunomodulant activity, as proved by its effect on both dendritic cell maturation in vitro and immune response in vivo (1). However, whether Sulfavant A has similar modulatory actions on microglia activation has not been investigated yet. Here, we studied whether Sulfavant A modulates M1 or M2 polarization by using BV2 microglial cell line. The effect of Sulfavant A was tested on lipopolysaccharide (LPS) (100 ng/mL)-induced microglia activation by evaluating the markers defining microglia phenotypes. Pre-incubation with Sulfavant A (10 ug/mL) for 30 minutes attenuated LPS-induced microglia activation, as demonstrated by reduction of Iba1 expression and M1 pro-inflammatory markers COX-2 and iNOS, whereas an upregulation of M2 markers, such as Arginase 1 , occurred. Accordingly, a reduction of the nitric oxide production was detected in supernatants of microglia cultures. Interestingly, Sulfavant A pre-incubation induced early (30 minutes) induction of ERK1/2 phosphorylation. Collectively, our data suggest that Sulfavant A may act as pro-homeostatic pharmacological tool for controlling neuroinflammation, interfering with M1 polarization but also rapidly activating intracellular pathways that may promote microglia phagocytosis without inflammation .