Cytosolic phospholipase A2α regulates induction of brain cyclooxygenase-2 in a mouse model of inflammation

Adam Sapirstein, Hideyuki Saito, Sarah J. Texel, Tarek A. Samad, Eileen O'Leary, Joseph V. Bonventre

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


The products of arachidonic acid metabolism are key mediators of inflammatory responses in the central nervous system, and yet we do not know the mechanisms of their regulation. The phospholipase A2 enzymes are sources of cellular arachidonic acid, and the enzymes cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) are essential for the synthesis of inflammatory PGE2 in the brain. These studies seek to determine the function of cytosolic phospholipase A (cPLA ) in inflammatory PGE2 production in the brain. We wondered whether cPLA functions in inflammation to produce arachidonic acid or to modulate levels of COX-2 or mPGES-1. We investigated these questions in the brains of wild-type mice and mice deficient in cPLA (cPLA-/-) after systemic administration of LPS. cPLA-/- mice had significantly less brain COX-2 mRNA and protein expression in response to LPS than wild-type mice. The reduction in COX-2 was most apparent in the cells of the cerebral blood vessels and the leptomeninges. The brain PGE2 concentration of untreated cPLA-/- mice was equal to their wild-type littermates. After LPS treatment, however, the brain concentration of PGE2 was significantly less in cPLA -/- than in cPLA+/+ mice (24.4 ± 3.8 vs. 49.3 ± 11.6 ng/g). In contrast to COX-2, mPGES-1 RNA levels increased equally in both mouse genotypes, and mPGES-1 protein was unaltered 6 h after LPS. We conclude that cPLA regulates COX-2 levels and, modulates inflammatory PGE2 levels. These results indicate that cPLA inhibition is a novel anti-inflammatory strategy that modulates, but does not completely prevent, eicosanoid responses.

Original languageEnglish (US)
Pages (from-to)R1774-R1782
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number6 57-6
StatePublished - Jun 2005


  • Inflammation
  • Lipopolysaccharide
  • Prostaglandin E
  • Prostaglandin E synthase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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