Eicosapentaenoic acid inhibits prostaglandin D₂ generation by inhibiting cyclo‐oxygenase‐2 in cultured human mast cells

Abstract

BACKGROUND: Eicosapentaenoic acid (EPA) is catalysed by cyclo-oxygenase (COX), as is arachidonic acid, and is a competitive inhibitor of arachidonate metabolism. OBJECTIVES: We examined the effect of EPA on prostaglandin (PG) D2 generation in the cultured human mast cells with IgE-anti-IgE challenge incubation. METHODS: Cultured human mast cells were incubated with EPA (1 micromol/L) for 20 h, then challenged with anti-IgE incubation after treatment with IgE. At the same time, COX inhibitors were tested to identify COX-1 and COX-2 activity. PGD2 synthetic activity was also assayed in a cell-free homogenate of cultured mast cells with COX inhibitors and EPA. Histamine in the culture medium and in cells was assayed with the HPLC-fluorescent method. PGD2 and PGD3 were assayed with gas chromatography-mass spectrometry and the stable isotope dilution method. RESULTS: Although EPA incubation did not affect histamine release by cultured human mast cells in response to IgE-anti-IgE challenge incubation, it did decrease PGD2 generation by inhibiting the COX-2 pathway. In contrast, in the cell-free homogenate of cultured human mast cells, EPA inhibited both COX-1 and COX-2 activities. CONCLUSION: Pre-incubation with EPA primarily affects the COX-2 pathway in cultured human mast cells and reduces PGD2 generation in response to IgE-anti-IgE challenge incubation. These findings suggest that COX-1 and COX-2 have different substrate flow systems in mast cells. They also suggest that endogenous EPA diet supplementation would reduce PGD2 production and could serve as an anti-inflammatory substrate in human mast cells.