N-3 polyunsaturated fatty acids (PUFA) modulate the expression of functionally associated molecules on human monocytes

Abstract

N-3 polyunsaturated fatty acid (PUFA)-rich diets are associated with suppression of the immune system and there is growing interest in the potential use of dietary fish oil [rich in the n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] supplementation in the treatment of disorders involving an overreactive immune response, such as rheumatoid arthritis [see 1 for review]. Although it has been shown that n-3 PUFAs can inhibit the proliferation of stimulated lymphocytes [see 2 for review], the mechanisms by which these fatty acids may depress immune responses remain unclear.Specific immune responses are initiated by the presentation of antigen to helper T-lymphocytes on the surface of an antigenpresenting cell (APC). A pre-requisite for this function of APCs is the cell surface expression of major histocompatibility complex (MHC) class I1 molecules, aided by the presence of adhesion molecules. It has been shown that the percentage of MHC class IIpositive monocytes and the density of these molecules on the cell surface can alter the degree of immune responsiveness of an individual [3].Increasing the PUFA content of plasma membranes increases their fluidity, and changes in this membrane property can lead to alterations in the expression of surface proteins [4]. We have previously shown that cholesterol, which rigidifies plasma membranes, can increase the expression of MHC class II molecules[ 5 ] , and we hypothesised that increasing the PUFA content may have an opposite effect. It has recently been reported that a fish oilrich diet can suppress the expression of MHC class I1 molecules on peritoneal cells from Listerio-infected mice [6] and that EPA can inhibit the antigen-presenting function of mouse splenocytes [7] but, to our knowledge, the effect of n-3 PUFAs on human APC has not been examined. In the present study both in vitro and dietary supplementation studies were performed to investigate the effects of n-3 PUFAs on the cell surface expression of MHC class I1 molecules and adhesion molecules by human blood monocytes.For the in vitro studies, purified monocytes, obtained from healthy volunteers, were incubated with or without EPA or DHA (20 pg/ml) in RPMI culture medium supplemented with 5% fetal calf serum for 48 h at 37°C. In addition, parallel cultures were performed in the presence of interferon-gamma (IFN-g; 400 U/ml) to stimulate upregulation of MHC class I1 molecule expression by the monocytes. Following incubation, the monocytes were immunofluorescently stained with monoclonal antibodies raised against the MHC class I1 molecules (HLA-DR, -DP and -DQ), and the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and leucocyte function associated antigen-l (LFA-1). Both the percentage of monocytes expressing each of these molecules and the intensity of exoression of each molecule was quantified by flow cytomeuy (51.In the Dresence of EPA alone, there was no significant difference in the pekentages of cells expressing each oflthe MHC class I1 molecules, but there was a signif...

Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders

“…After 24 weeks, a fall in the proportion of peripheral blood CD4 + cells and an increase in CD8 + cells was observed (Meydani et al 1993). Supplementation with n-3 PUFA depressed immune reactivity in volunteers by suppressing the expression of monocyte surface molecules associated with their antigenpresenting function (Hughes et al 1995).…”

Fish oil and the immune system

“…The major PUFA present in fish oil, eicosapentaenoic acid (EPA), can inhibit antigen‐presenting cell function in mice, and we have shown that, after a three‐week period of dietary fish oil supplementation (3g/day), monocytes from healthy human volunteers exhibited a significant reduction in the expression of the cell surface molecules involved in this process[4]. At the Institute of Food Research we have also shown that EPA can inhibit the expression of these surface molecules on human monocytes in vitro .…”

The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease

“…n3-PUFAs can regulate the transcription and expression of inflammatory mediators such as cytokines, chemokines and adhesion molecules in cardiomyocytes, fibroblasts, endothelial cells, and monocyte-macrophages ( 101 – 104 ). Anti-inflammatory effect of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and their biologically active metabolites (D and E Resolvins - mediators derived from omega-3 fatty acids, primarily EPA and DHA that block the production of proinflammatory mediators and regulate leukocyte trafficking to inflammatory sites) can be mediated through one of the mechanisms capable of reducing inflammation of RAW-264.7 cells and of primary intraperitoneal macrophages ( 105 ).…”