Pheophytin a and chlorophyll a suppress neuroinflammatory responses in lipopolysaccharide and interferon-γ-stimulated BV2 microglia

Aims: Microglia-mediated inflammation is associated with pathogenesis of various neuronal disorders. This study investigated inhibitory effects of pheophytin a (PP) and chlorophyll a (CP) on neuroinflammation and underlying cellular mechanisms in microglia cells. Main methods: BV2 murine microglia cells were stimulated by lipopolysaccharide (LPS, 100 ng/mL) and interferon (IFN)-gamma (10 U/mL). The productions of nitric oxide (NO) and expressions of proinflammatory cytokines and chemokines were determined by ELISA and RT-PCR. Western blot and confocal microscopy were applied to analyze activation of transcription factors and mitogen activated protein kinase (MAPK). Key findings: PP and CP significantly reduced the levels of NO, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6 and chemokines including macrophage inhibitory protein (MIP)-1 alpha, macrophage chemoattractant protein (MCP)-1 and IFN-gamma inducible protein (IP)-10 in BV2 cells stimulated with LPS and IFN-gamma (LI). The nuclear expression of p65 NF-kappa B was significantly suppressed, which was accompanied by reduced the levels of IFN-beta, phospho-STAT-1, and interferon regulatory factor (IRF)-1. Activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) but not p38 MAPK were prominently suppressed by PP and/or CP. Significance: PP and CP may suppress inflammatory responses by inhibiting NF-kappa B activation and type I IFN signaling pathway. These result suggested that PP and CP have potential as anti-inflammatory agents for microglia-mediated neuroinflammatory disorders. (C) 2014 Elsevier Inc All rights reserved.