(+)-JQ1 attenuated LPS-induced microglial inflammation via MAPK/NFκB signaling

Microglia activation is a crucial event in neurodegenerative disease. The depression of microglial inflammatory response is considered a promising therapeutic strategy. NF kappa B signaling, including IKK/I kappa B phosphotylation, p65 nucelus relocalization and NF kappa B-related genes transcription are prevalent accepted to play important role in microglial activation. (+)-JQ1, a BRD4 inhibitor firstly discovered as an anti-tumor agent, was later confirmed to be an anti-inflammatory compound. However, its anti-inflammatory effect in microglia and central neural system remains unclear. In the current work, microglial BV2 cells were applied and treatment with lipopolysaccharide (LPS) to induce inflammation and later administered with (+)-JQ1. In parallel, LPS and (+)-JQ1 was intracerebroventricular injected in IL-1 beta-luc transgenic mice, followed by fluorescence evaluation and brain tissue collection. Results showed that (+)-JQ1 treatment could significantly reduce LPS induced transcription of inflammatory cytokines both in vitro and in vivo. (+)-JQ1 could inhibit LPS induced MAPK but not PI3K signaling phosphorylation, NF kappa B relocalization and transcription activity. In animal experiments, (+)-JQ1 postponed LPS induced microglial and astrocytes activation, which was also dependent on MAPK/NF kappa B signaling. Thus, our data demonstrated that (+)-JQ1 could inhibit LPS induced microglia associated neuroinflammation, via the attenuation of MAPK/NF kappa B signaling.