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Dietary marine lipids suppress continuous expression of interleukin‐1β gene transcription 1
Author(s) -
Robinson Dwight R.,
Urakaze Masaharu,
Huang Riyun,
Taki Hirofumi,
Sugiyama Eiji,
Knoell Christopher T.,
Xu LiLian,
Yeh Edward T. H.,
Auron Philip E.
Publication year - 1996
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02637046
Subject(s) - fish oil , polyunsaturated fatty acid , lipopolysaccharide , biology , fatty acid , peripheral blood mononuclear cell , cytokine , gene expression , spleen , lipogenesis , messenger rna , biochemistry , phorbol , medicine , endocrinology , microbiology and biotechnology , lipid metabolism , immunology , in vitro , gene , enzyme , protein kinase c , fishery , fish <actinopterygii>
Abstract n‐3 Polyunsaturated fatty acids abundant in marine lipids suppress certain inflammatory and immune reactions, and dietary marine lipid supplements have antiinflammatory effects in experimental and human autoimmune disease. Previous work by other investigators demonstrated that dietary marine lipid supplements suppressed production of cytokines from stimulated human peripheral blood mononuclear cells ex vivo . The present study further documents the ability of n‐3 fatty acids to inhibit cytokine formation, and in part defines the mechanism of the inhibition of production of interleukin‐1β (IL‐1β) by dietary n‐3 fatty acid. Female BALB/c mice were each fed a fatfree balanced diet to which was added either a refined fish oil (FO) preparation as a source of n‐3 fatty acid, or beef tallow (BT), which consisted primarily of saturated and monoenoic fatty acids. After ingesting the experimental diets for periods ranging from 3 to 12 wk, spleen cell preparations were stimulated ex vivo with either lipopolysaccharide (LPS) or phorbol 12‐myristate 13‐acetate (PMA), and prolL‐1β mRNA (Il‐1β mRNA) was measured by northern analysis. Levels of IL‐1β mRNA in both LPS‐and PMA‐stimulated cells from BT‐fed mice were elevated to a greater extent than in cells from FO‐fed mice, at most concentrations of LPS and PMA. Stability of LPS‐stimulated mRNA levels after actinomycin D was similar for BT and FO groups, indicating that lower levels of IL‐1 mRNA with FO groups was related to suppressed IL‐1 gene transcription and not due to accelerated transcript degradation. Nuclear run‐on transcription assays revealed a more transient expression of the IL‐1β gene in LPS‐stimulated spleen cells from FO‐fed mice compared to cells from BT‐fed mice. We conclude that dietary marine lipids reduce transient expression of the IL‐1β gene in stimulated splenic monocytic cells. Preliminary results from nuclear run‐on transcription assays indicate that n‐3 fatty acids may not change the initial rate of gene transcription but may promote more rapid shutting down of transcription of this gene after induction than do alternative lipids.