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  • Eicosapentaenoic acid suppresses palmitate-induced cytokine production by modulating long-chain acyl-CoA synthetase 1 expression in human THP-1 macrophages.

Eicosapentaenoic acid suppresses palmitate-induced cytokine production by modulating long-chain acyl-CoA synthetase 1 expression in human THP-1 macrophages.

Atherosclerosis (2013-02-26)
Masanori Nakakuki, Hiroyuki Kawano, Tatsuto Notsu, Kazunori Imada
ABSTRACT

Chronic inflammation caused by macrophages may be associated with progression of arteriosclerosis or obesity, both risk factors for cardiovascular events. In the Japan EPA Lipid Intervention Study (JELIS), eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid, was found to reduce the incidence of cardiovascular events. The effect of EPA on the expression of inflammatory factors induced by palmitate, a saturated fatty acid, was investigated using human THP-1 macrophages. Palmitate induced expression of inflammatory cytokines and activated NF-κB, similar to lipopolysaccharide (LPS). EPA strongly suppressed palmitate-induced up-regulation of inflammatory factors while slightly suppressing LPS-induced factors. Both palmitate and LPS up-regulated expression of long-chain acyl-CoA synthetase (ACSL) 1, while EPA preferentially suppressed palmitate-induced ACSL1 expression. Although an acyl-CoA synthetase inhibitor and ACSL1 siRNA both suppressed palmitate-induced tumor necrosis factor (TNF)-α expression, the former had no effect on LPS-induced TNF-α expression. Palmitate may therefore stimulate cytokine production through a different mechanism than LPS mediated through Toll-like receptor 4, at least partly, and ACSL1 may play an important role in this mechanism. Finally, palmitate induced expression of sterol regulatory element-binding protein-1a and ACSL1, while EPA suppressed the expression of these genes. The suppressive effects of EPA on palmitate-induced cytokine production may be mediated by the suppression of ACSL1 expression, at least partly. This anti-inflammatory effect of EPA may contribute to suppression of chronic inflammation caused by macrophages in atherosclerotic plaques.

MATERIALS
Product Number
Brand
Product Description

Palmitic acid, European Pharmacopoeia (EP) Reference Standard
Supelco
Palmitic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Palmitic acid, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
Palmitic acid, natural, 98%, FG
Sigma-Aldrich
Palmitic acid, BioXtra, ≥99%
Sigma-Aldrich
Palmitic acid, ≥98% palmitic acid basis (GC)
Sigma-Aldrich
Palmitic acid, ≥98%, FCC, FG
Sigma-Aldrich
Palmitic acid, ≥99%
Supelco
Palmitic acid, analytical standard