The Combined Effects of Lysophospholipids against Lipopolysaccharide-induced Inflammation and Oxidative Stress in Microglial Cells
Tamotsu Tsukahara, Hiroto Hara, Hisao Haniu, Yoshikazu Yonei
Abstract
Lysophospholipids (LPLs) are small bioactive lipid molecules characterized by a single carbon chain and a polar head group. LPLs have recently shown to be involved in many physiological and pathological processes such as nervous system regulation. In our previous studies, a porcine liver decomposition product (PLDP) has been identified as a substance that improves cognitive function at old ages. This PLDP is a rich source of LPLs, including lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). This study was designed to evaluate the anti-inflammatory effect of these LPLs on lipopolysaccharide (LPS)-stimulated SIM-A9 microglial cells in terms of cytokine expression and oxidative stress and to investigate the potential mechanisms underlying these effects. SIM-A9 cells were pretreated with LPLs prior to LPS stimulation, and the anti-inflammatory potential of the LPLs in LPS-induced SIM-A9 cells was examined. Pretreatment with LPLs significantly inhibited the LPS-induced expression of IL-6 in SIM-A9 cells. Furthermore, oxidative-related protein, NADPH oxidase 2 (Nox2) levels were markedly increased in the LPS-treated cells, and pretreatment with LPC and LPE significantly reduced to basal levels. In addition, LPS-induced ROS production was eliminated in apocynin-treated cells, indicating that ROS production was dependent on Nox2. Our findings revealed that pretreatment with LPC and LPE decreased LPS-stimulated ROS production. These results indicated that LPC and LPE exerted significant protective effects against LPS-induced inflammation and oxidative stress in SIM-A9 cell.