Dietary marine lipids suppress continuous expression of interleukin‐1β gene transcription¹

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-1 beta (IL-1 beta) by dietary n-3 fatty acid. Female BALB/c mice were each fed a fat-free 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 proIL-1 beta mRNA (IL-1 beta mRNA) was measured by northern analysis. Levels of IL-1 beta 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-1 beta 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-1 beta 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.

Regulation of sodium channel gene expression by class I antiarrhythmic drugs and n − 3 polyunsaturated fatty acids in cultured neonatal rat cardiac myocytes

“…The multiple (diverse) biological effects of n Ϫ 3 fatty acids render them able to affect gene expression through different pathways or at different levels. In fact, PUFA have recently been shown to suppress the expression of a number of genes in other tissues (25)(26)(27)(28)(29), although the mechanism of their action remains unclear.…”

Dietary modification of inflammation with lipids

“…Inclusion of fish oil in the diet completely abolished mRNA for TNF-α, IL-1β and IL-6 in the kidneys of autoimmune disease-prone mice (Chandrasekar & Fernandes, 1994). Feeding wild-type mice a fish oil-rich diet decreased the level of IL-1β mRNA in LPS-or phorbol ester-stimulated spleen lymphocytes (Robinson et al 1996); the lower IL-1β mRNA level was not due to accelerated degradation but to impaired synthesis. Fish oil feeding to mice lowered basal and LPS-stimulated TNF-α mRNA levels in peritoneal macrophages (Renier et al 1993).…”

Guide and Position of the International Society of Nutrigenetics/Nutrigenomics on Personalised Nutrition: Part 1 - Fields of Precision Nutrition

“…Nutrigenomic strategies thus include analysis of gene expression and biochemical profiles. Early examples of such research strategies include the finding that dietary cholesterol inhibits transcription of the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene [56], and that long-chain omega-3 polyunsaturated fatty acids reduce gene transcription of platelet-derived growth factor and interleukin-1β [57,58]. …”