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Eicosapentaenoic acid inhibits prostaglandin D 2 generation by inhibiting cyclo‐oxygenase‐2 in cultured human mast cells
Author(s) -
Toru Obata,
Toshikazu Nagakura,
Takuro Masaki,
Kihei Maekawa,
Kouwa Yamashita
Publication year - 1999
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.1999.00604.x
Subject(s) - histamine , prostaglandin d2 , mast cell , eicosapentaenoic acid , immunoglobulin e , incubation , arachidonic acid , prostaglandin , biochemistry , cell culture , biology , chemistry , pharmacology , microbiology and biotechnology , immunology , fatty acid , enzyme , antibody , polyunsaturated fatty acid , genetics
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) D 2 generation in the cultured human mast cells with IgE‐anti‐IgE challenge incubation. Methods Cultured human mast cells were incubated with EPA (1 μmol/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. PGD 2 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. PGD 2 and PGD 3 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 PGD 2 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 PGD 2 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 PGD 2 production and could serve as an anti‐inflammatory substrate in human mast cells.