A ceramide analog inhibits cPLA 2 activity and consequent PGE 2 formation in LPS-stimulated macrophages

Meir Goldsmith, Ala Daka, Nadia F. Lamour, Roi Mashiach, Yifat Glucksam, Michael M. Meijler, Charles E. Chalfant, Tsaffrir Zor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Prostaglandin E 2 (PGE 2) is an important mediator of the inflammatory response. Phospho-ceramide analogue-1 (PCERA-1), a synthetic phospholipid-like molecule, was previously reported to modulate pro- and anti-inflammatory cytokine production. We show here that PCERA-1 inhibited LPS-stimulated PGE 2 production in RAW264.7 macrophages, without affecting COX-2 expression. Furthermore, PCERA-1 efficiently suppressed arachidonic acid (AA) release in response to LPS. The dephosphorylated derivative of PCERA-1, ceramide analogue-1 (CERA-1), mimicked the inhibitory effect of PCERA-1 on AA release and PGE 2 production in macrophages. Inhibition of PGE 2 production by CERA-1 was completely rescued by addition of exogenous AA. Importantly, PCERA-1 and ceramide-1-phosphate (C1P) stimulated the enzymatic activity of cPLA 2α in an in vitro assay, whereas CERA-1 and ceramide inhibited both basal and C1P-stimulated cPLA 2α activity. Collectively, these results indicate that CERA-1 suppresses AA release and subsequent PGE 2 production in LPS-stimulated macrophages by direct interaction with cPLA 2, and suggest that ceramide may similarly counteract C1P effect on cPLA 2 activity in cells. The suppression of PGE 2 production is suggested to contribute to the anti-inflammatory action of PCERA-1.

Original languageEnglish
Pages (from-to)136-143
Number of pages8
JournalImmunology Letters
Issue number1-2
StatePublished - 30 Mar 2011


FundersFunder number
Veteran's Administration
National Institutes of HealthHL072925
National Cancer InstituteR01CA117950
European Commission021862


    • Arachidonic acid
    • Ceramide
    • Ceramide-1-phosphate
    • LPS
    • Phospholipase A
    • Prostaglandin E


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