n-3 Polyunsaturated fatty acid-enriched phosphatidylglycerol suppresses inflammation in RAW264.7 cells through Nrf2 activation via alteration of fatty acids in cellular phospholipids

摘要

Phosphatidylglycerol (PG) is a naturally occurring phospholipid. The immunomodulatory activity of PG has been reported to be dependent on its fatty acid composition. In this study, the anti-inflammatory effect of n-3 polyunsaturated fatty acid-enriched PG (n-3 PUFA-PG) was investigated on macrophage-like RAW264.7 cells stimulated by lipopolysaccharide (LPS). n-3 PUFA-PG binding eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) significantly suppressed interleukin-6, interleukin-1 β and nitric oxide production by RAW264.7 cells. Notably, the suppressive effect of n-3 PUFA-PG on inflammatory factor production was more potent compared to n-3 PUFA-phosphatidylcholine (PC) and soybean PG. n-3 PUFA-PG treatment markedly increased EPA and DHA in intracellular PC and phosphatidylethanolamine and decreased 18:1n-9 through downregulation of fatty acid synthase and stearoyl-CoA desaturase mRNA expression compared to n-3 PUFA-PC treatment. Furthermore, n-3 PUFA-PG enhanced nuclear factor erythroid E2-related factor (Nrf2) levels in the nucleus and increased heme oxygenase-1 mRNA expression. N-acetyl-L-cysteine, which is an inhibitor against Nrf-2 activation, alleviated the induction of HO-1 mRNA and anti-inflammatory effect of n-3 PUFA-PG. These data suggest that n-3 PUFA-PG exhibits anti-inflammatory effects on LPS-stimulated RAW264.7 cells through Nrf2 activation by altering cellular fatty acids.