Effects of in vitro exposure to arachidonic acid on TNF-α production by murine peritoneal macrophages

Neil Hubbard, D. Lim, S. D. Somers, Kent L Erickson

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Abstract

Modifying the fatty acid composition of macrophages through diet can significantly alter some of their functions, such as tumoricidal capacity and tumor necrosis factor α (TNF-α) production. The mechanism of that modification, however, is unknown. In this report, we provide evidence that fatty acids added to macrophages in culture can significantly alter macrophage TNF-α production. For example when inflammatory macrophages were incubated with various doses of arachidonic acid [20:4(n-6)] during activation with lipopolysaccharide (LPS), we observed a dose-dependent decrease in the level of bioactive TNF-α with complete inhibition at 2-5 μM. This inhibition was specific for 20:4(n-6) because in vitro treatment with other fatty acids, such as eicosapentaenoic [20:5(n-3)] or docosahexaenoic [22:6(n-3)] acids, had differential effects. The inhibitory action of 20:4(n-6) did not involve toxicity because cell viability was not affected and in vitro interferon-γ and lipopolysaccharide (LPS) activation of macrophages for killing of P815 tumor targets was not altered. Inhibition by 20:4(n-6) occurred posttranscriptionally, and could be reversed when macrophages were treated with indomethacin during activation. Arachidonic acid treatment also significantly increased the production of immunoreactive prostaglandin E2 (PGE2) by LPS-treated and untreated macrophages. These results suggest that in vitro treatment of macrophages with 20:4(n-6) may inhibit TNF-α production through an alteration in the levels of PGE2 at a posttranscriptional level. These results provide evidence that some dietary fats may affect macrophage activity through modification of eicosanoid synthesis.

Original languageEnglish (US)
Pages (from-to)105-110
Number of pages6
JournalJournal of Leukocyte Biology
Volume54
Issue number2
StatePublished - 1993

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Keywords

  • arachidonic acid
  • macrophages
  • prostaglandins
  • tumor necrosis factor

ASJC Scopus subject areas

  • Cell Biology

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