Inhibition of Lipopolysaccharide-Induced Inflammatory Signaling by Soft Coral-Derived Prostaglandin A2 in RAW264.7 Cells.

Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria and causes inflammatory diseases. We searched MeOH extracts of collected marine organisms for inhibitors of LPS-induced nitric oxide (NO) production in RAW264.7 cells and identified prostaglandin A2 (PGA2) as an active compound from the MeOH extract of the soft coral Lobophytum sp. PGA2 inhibited the production of NO and reduced the expression of inducible NO synthase (iNOS) in LPS-stimulated RAW264.7 cells. Although short preincubation with PGA2 did not inhibit LPS-induced degradation and resynthesis of IκBα, the suppressive effect of PGA2 was observed only after a prolonged incubation period prior to LPS treatment. In addition, PGA2-inhibited NO production was negated by the addition of the EP4 antagonist L161982. Thus, PGA2 was identified as an inhibitor of LPS-induced inflammatory signaling in RAW264.7 cells.