Ajulemic acid, a synthetic cannabinoid, increases formation of the endogenous proresolving and anti-inflammatory eicosanoid, lipoxin A4

Robert B. Zurier, Yee Ping Sun, Kerri L. George, Judith A. Stebulis, Ronald G. Rossetti, Ann Skulas, Erica Judge, Charles N. Serhan

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Ajulemic acid (AjA), a synthetic nonpsychoactive cannabinoid, and lipoxin A4 (LXA4), an eicosanoid formed from sequential actions of 5- and 15-lipoxygenases (LOX), facilitate resolution of inflammation. The purpose of this study was to determine whether the ability of AjA to limit the progress of inflammation might relate to an increase in LXA4, a known anti-inflammatory and proresolving mediator. Addition of AjA (0-30 μM) in vitro to human blood and synovial cells increased production of LXA4 (ELISA) 2- to 5-fold. Administration of AjA to mice with peritonitis resulted in a 25-75% reduction of cells invading the peritoneum, and a 7-fold increase in LXA4 identified by mass spectrometry. Blockade of 12/15 LOX, which leads to LXA4 synthesis via 15-HETE production, reduced (>90%) the ability of AjA to enhance production of LXA4 in vitro. These results suggest that AjA and other agents that increase endogenous compounds that facilitate resolution of inflammation may be useful for conditions characterized by inflammation and tissue injury.

Original languageEnglish (US)
Pages (from-to)1503-1509
Number of pages7
JournalFASEB Journal
Volume23
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

Keywords

  • Arthritis
  • Lipoxygenase
  • Nephritis
  • Resolution

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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