Abstract
Fatty acid composition of human immune cells influences their function. The aim of this study was to evaluate the effects of known toxicant and immunomodulator, cadmium, at low concentrations on levels of selected fatty acids (FAs) in THP-1 macrophages. The differentiation of THP-1 monocytes into macrophages was achieved by administration of phorbol myristate acetate. Macrophages were incubated with various cadmium chloride (CdCl2) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM, and 2 μM CdCl2. Fatty acids were extracted from samples according to the Folch method. The fatty acid levels were determined using gas chromatography. The following fatty acids were analyzed: long-chain saturated fatty acids (SFAs) palmitic acid and stearic acid, very long-chain saturated fatty acid (VLSFA) arachidic acid, monounsaturated fatty acids (MUFAs) palmitoleic acid, oleic acid and vaccenic acid, and n-6 polyunsaturated fatty acids (PUFAs) linoleic acid and arachidonic acid. Treatment of macrophages with very low concentrations of cadmium (5–200 nM) resulted in significant reduction in the levels of arachidic, palmitoleic, oleic, vaccenic, and linoleic acids and significant increase in arachidonic acid levels (following exposure to 5 nM Cd), without significant reduction of palmitic and stearic acid levels. Treatment of macrophages with the highest tested cadmium concentration (2 μM) produced significant reduction in the levels of all examined FAs: SFAs, VLSFA, MUFAs, and PUFAs. In conclusion, cadmium at tested concentrations caused significant alterations in THP-1 macrophage fatty acid levels, disrupting their composition, which might dysregulate fatty acid/lipid metabolism thus affecting macrophage behavior and inflammatory state.
Highlights
IntroductionFatty acids (FAs) play multiple roles in immune cells, including serving as fuels for energy generation, contributing to physical and functional properties of cell membranes (as components of cell membrane phospholipids), or being covalent modifiers of protein structure
Fatty acids (FAs) play multiple roles in immune cells, including serving as fuels for energy generation, contributing to physical and functional properties of cell membranes, or being covalent modifiers of protein structure
In one of our previous studies, we examined one of the possible mechanisms involved in inflammatory reaction of THP-1 macrophages exposed to low concentrations of cadmium for 48 h: cadmium effects on COX-1 and COX-2 at messenger RNA, protein, and enzymatic activity levels [22]
Summary
Fatty acids (FAs) play multiple roles in immune cells, including serving as fuels for energy generation, contributing to physical and functional properties of cell membranes (as components of cell membrane phospholipids), or being covalent modifiers of protein structure. Fatty acids are regulators of gene expression acting either on receptor activity, intracellular signaling, or transcription factor activation. Fatty acid composition of human immune cells influences their function via a variety of ways, including membrane alterations, effects on signal transduction pathways, or alterations in lipid mediators’ patterns [1]. Long-chain saturated fatty acids (SFAs), such as palmitic acid and stearic acid, have been found to produce a proinflammatory effect on several cell types, including human macrophages, inducing different inflammatory pathways [5, 9, 10] A number of studies, both in vivo and in vitro, examined the effects of enrichment with different fatty acids on fatty acid profile in different cells, on cell function and behavior, and/or on different processes, such as inflammation [1,2,3,4,5,6,7,8,9,10,11].
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