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Regulation by dietary essential fatty acid balance of tumor necrosis factor production in mouse macrophages
Author(s) -
Watanabe Shiro,
Onozaki Kikuo,
Yamamoto Shunsuke,
Okuyama Harumi
Publication year - 1993
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.53.2.151
Subject(s) - tumor necrosis factor alpha , lipopolysaccharide , biology , macrophage , prostaglandin e2 , endocrinology , casein , medicine , biochemistry , in vitro
Abstract Increasing die dietary α‐linolenate (18:3n ‐ 3)/linoleate (18:2n ‐ 6) ratio results in an increase in lipopolysaccharide (LPS)‐etimulated tumor necrosis factor (TNF) production in mouse resident and casein‐induced peritoneal macrophages [3]. We found that prostaglandin E2 (PGE2) production is inversely related to TNF production and that indomethacin abolishes the effect of changing the essential fatty add balance in resident macrophages. The resident macrophages enriched in n ‐ 3 did not produce a significant amount of PGE3. Accordingly, the decreased production of PGE2 appears to be a major negative regulatory factor for enhancement of TNF production in the it ‐ 3 enriched resident macrophages. In casein‐induced macrophages the situation is more complex. Indomethadn decreased PGE2 production and increased TNF production; however, the differences in TNF production between the it ‐ 6 enriched and it ‐ 3 enriched macrophages were not completely abolished by indomethadn treatment. Lysosomal add phosphatase activity, a marker of activation/maturation stages, was elevated in the it ‐ 3 enriched compared to the it ‐ 6 enriched casein‐induced macrophages but was similar in the resident macrophages of the two dietary groups. Expression of CD 14, which is a receptor for LPS, was not different in casein‐induced macrophages of the two dietary groups. Thus, the differences in production of TNF between the n ‐ 3 and n ‐ 6 enriched resident macrophages can he accounted for mostly by a difference in the production of a negative feedback effector, PGE2. However, a significant portion of the TNF production in casein‐induced macrophages is regulated by a factor(s) other than PGE2 and LPS receptor; advanced activation/maturation stages induced by the diet high in α‐linolenate may underlie the enhanced TNF production in casein‐induced macrophages.