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Ajulemic acid, a synthetic cannabinoid, increases formation of the endogenous proresolving and anti‐inflammatory eicosanoid, lipoxin A4
Author(s) -
Zurier Robert B.,
Sun YeePing,
George Kerri L.,
Stebulis Judith A.,
Rossetti Ronald G.,
Skulas Ann,
Judge Erica,
Serhan Charles N.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-118323
Subject(s) - lipoxin , inflammation , eicosanoid , lipid signaling , endogeny , chemistry , endocannabinoid system , in vitro , pharmacology , biochemistry , immunology , arachidonic acid , biology , receptor , enzyme
Ajulemic acid (AjA), a synthetic nonpsychoactive cannabinoid, and lipoxin A4 (LXA 4 ), 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 LXA 4 , a known antiinflammatory and proresolving mediator. Addition of AjA (0‐30 p, M) in vitro to human blood and synovial cells increased production of LXA 4 (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 LXA 4 identified by mass spectrometry. Blockade of 12/15 LOX, which leads to LXA 4 synthesis via 15‐HETE production, reduced (>90%) the ability of AjA to enhance production of LXA 4 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.— Zurier, R. B., Sun, Y.‐P., George, K. L., Stebu‐lis, J. A., Rossetti, R. G., Skulas, A., Judge, E., Serhan, C. N. Ajulemic acid, a synthetic cannabinoid, increases formation of the endogenous proresolving and antiinflammatory eicosanoid, lipoxin A4. FASEB J . 23, 1503–1509 (2009)