Effect of Dihomogammalinolenic Acid and Its 15-lipoxygenase Metabolite on Eicosanoid Metabolism by Human Mononuclear Leukocytes in Vitro: Selective Inhibition of the 5-lipoxygenase Pathway

Overview

Journal Arch Dermatol Res

Specialty Dermatology

Date 1992 Jan 1

PMID 1329675

Citations 15

Authors

L Iversen

K Fogh

K Kragballe

Affiliations

Soon will be listed here.

Abstract

The purpose of the present study was to determine the effect of the n-6 fatty acid, dihomogammalinolenic acid (DGLA, 20: 3, n-6) on arachidonic acid (AA) (C20: 4) metabolism by human peripheral mononuclear leukocytes (HPML). After incubation of HPML with A23187 (5 microM) and DGLA, the cyclooxygenase (CO) and lipoxygenase (LO) products were separated and quantified by reversed-phase high-performance liquid chromatography (RP-HPLC) combined with radioimmunoassay. DGLA led to no change in PGE2 formation, but at similar concentrations there was a dose-dependent decrease in LTB4 formation (IC50 = 45.0 microM). The inhibition of LTB4 formation by DGLA was associated with a dose-dependent increase in its 15-LO metabolite 15-hydroxyeicosatraenoic acid (15-HETrE) and its CO metabolite prostaglandin E1 (PGE1). Incubation of HPLM with 15-HETrE (0-1.5 microM) alone did not result in a change in PGE2 formation, whereas 15-HETrE was a much more potent inhibitor of LTB4 formation (IC50 = 0.5 microM) than DGLA. These results show that the addition of DGLA to HPML results in a selective inhibition of LTB4 formation, presumably via its metabolite (15-HETrE).

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