Inhibition of Lipopolysaccharide-Induced Inflammatory Signaling by Soft Coral-Derived Prostaglandin A(2) 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 A(2) (PGA(2)) as an active compound from the MeOH extract of the soft coral Lobophytum sp. PGA(2) inhibited the production of NO and reduced the expression of inducible NO synthase (iNOS) in LPS-stimulated RAW264.7 cells. Although short preincubation with PGA(2) did not inhibit LPS-induced degradation and resynthesis of IκBα, the suppressive effect of PGA(2) was observed only after a prolonged incubation period prior to LPS treatment. In addition, PGA(2)-inhibited NO production was negated by the addition of the EP4 antagonist L161982. Thus, PGA(2) was identified as an inhibitor of LPS-induced inflammatory signaling in RAW264.7 cells.