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Eicosapentaenoic (EPA) and Docosahexaenoic (DHA) Acid Differentially Modulate Rat Neutrophil Function In Vitro

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Lipids

Abstract

Fish oils are used as therapeutic agents in chronic inflammatory diseases. The omega-3 fatty acids (FA) found in these oils are mainly eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. The anti-inflammatory properties of fish oils are attributed to both omega-3 fatty acids. However, it is unknown whether such effects are due to either EPA or DHA. In this study, the effects of EPA and DHA on rat neutrophil function in vitro were compared. Both EPA and DHA increased the production of H2O2 when cells were stimulated or not with lipopolysaccharides (LPS). However, EPA was more potent than DHA in triggering an increase in superoxide release by cells in the basal condition or when stimulated with phorbol myristate acetate (PMA) or zymosan. Only DHA increased the phagocytic capacity and fungicidal activity of neutrophils. Both FA increased the release of tumor necrosis factor-α (TNF-α) in nonstimulated cells, but only EPA increased the production of cytokine-inducing neutrophil chemoattractant-2 (CINC-2) in the absence or presence of LPS, whereas production of interleukin-1 beta (IL-1β) was only increased by DHA in the presence of LPS. In addition, there was no alteration in the production of nitric oxide. In conclusion, we show herein that EPA and DHA can differently modulate aspects of the neutrophil response, which may be relevant for the development of therapies rich in one or other FA depending on the effect required.

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Abbreviations

ANOVA:

Analysis of variance

CINC-2:

Cytokine-inducing neutrophil chemoattractant-2

DHA:

Docosahexaenoic acid

DPI:

Diphenyliodonium

ELISA:

Enzyme-linked immunosorbent assay

EPA:

Eicosapentaenoic acid

FA:

Fatty acid

FBS:

Fetal bovine serum

fMLP:

N-formyl-methionyl-leucyl-phenylalanine

HEPES:

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

HRP:

Horseradish peroxidase

IL-1β:

Interleukin-1 beta

LPS:

Lipopolysaccharides

NADPH:

Reduced nicotinamide adenine dinucleotide phosphate

NLR:

Nucleotide-binding protein oligomerization domain

PBS:

Phosphate-buffered saline

PMA:

Phorbol myristate acetate

PUFA:

Polyunsaturated fatty acid

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

RPMI:

Roswell park memorial institute

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

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Acknowledgments

This study is supported by FAPESP, CNPq, and CAPES. The authors acknowledge the technical support of José Roberto Mendonça.

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Correspondence to V. A. Paschoal.

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Paschoal, V.A., Vinolo, M.A.R., Crisma, A.R. et al. Eicosapentaenoic (EPA) and Docosahexaenoic (DHA) Acid Differentially Modulate Rat Neutrophil Function In Vitro. Lipids 48, 93–103 (2013). https://doi.org/10.1007/s11745-012-3726-6

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