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.