Abstract
Nutritional fatty acids are known to have an impact on membrane lipid composition of body cells, including cells of the immune system, thus providing a link between dietary fatty acid uptake, inflammation and immunity. In this study we reveal the significance of macrophage membrane lipid composition on gene expression and cytokine synthesis thereby highlighting signal transduction processes, macrophage activation as well as macrophage defense mechanisms. Using RAW264.7 macrophages as a model system, we identified polyunsaturated fatty acids (PUFA) of both the n-3 and the n-6 family to down-regulate the synthesis of: (i) the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α; (ii) the co-stimulatory molecule CD86; as well as (iii) the antimicrobial polypeptide lysozyme. The action of the fatty acids partially depended on the activation status of the macrophages. It is particularly important to note that the anti-inflammatory action of the PUFA could also be seen in case of infection of RAW264.7 with viable microorganisms of the genera R. equi and P. aeruginosa. In summary, our data provide strong evidence that PUFA from both the n-3 and the n-6 family down-regulate inflammation processes in context of chronic infections caused by persistent pathogens.
Highlights
Fatty acids are an integral part of cellular membranes
Stimulation of RAW264.7 with lipopolysaccharide (LPS), phorbol-12-myristate-13-acetate (PMA), P. aeruginosa and R. equi respectively induced an increase in the concentration of pro-inflammatory cytokines in cell supernatants (Figure 1)
oxododecanoyl-L-homoserine lactone (OdDHL) abrogated the stimulating effect of LPS on IL-1β, IL-6 and TNF-α synthesis (Figure 1)
Summary
Fatty acids are an integral part of cellular membranes. The heterogeneity of fatty acids in the membrane contributes to membrane fluidity as well as to the physical and chemical properties of various membrane domains [1,2]. R. equi, a Gram-positive, aerobic, facultative intracellular and immotile soil bacterium, is known as a pulmonary pathogen of young horses and immunocompromised humans, such as AIDS patients [13,14,15]. There are both virulent and non-virulent isolates. Virtually no data regarding the relevance of PUFA in case of macrophage infection with R. equi or P. aeruginosa exist In this in vitro-study under defined conditions, we reveal the implication of stimulation and PUFA supplementation on key proteins of innate immune response
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