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

OBJECTIVE

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.

METHODS

BV2 murine microglia cells were stimulated by lipopolysaccharide (LPS, 100 ng/mL) and interferon (IFN)-γ (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).

RESULTS

PP and CP significantly reduced the levels of NO, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and chemokines including macrophage inhibitory protein (MIP)-1α, macrophage chemoattractant protein (MCP)-1 and IFN-γ inducible protein (IP)-10 in BV2 cells stimulated with LPS and IFN-γ (LI). The nuclear expression of p65 NF-κB was significantly suppressed, which was accompanied by reduced the levels of IFN-β, 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.

CONCLUSIONS

PP and CP may suppress inflammatory responses by inhibiting NF-κB 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.