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Enhanced production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in very long chain saturated fatty acid-accumulated macrophages

Naotake Yanagisawa12, Kazunori Shimada1*, Tetsuro Miyazaki1, Atsumi Kume1, Yohei Kitamura2, Katsuhiko Sumiyoshi1, Takashi Kiyanagi1, Takafumi Iesaki3, Nao Inoue1 and Hiroyuki Daida1

Author Affiliations

1 Department of Cardiovascular Medicine, Juntendo University School of Medicine, Tokyo, Japan

2 Nutritional Science Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan

3 Department of Organ and Cell Physiology, Juntendo University School of Medicine, Tokyo, Japan

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Lipids in Health and Disease 2008, 7:48  doi:10.1186/1476-511X-7-48

Published: 28 November 2008

Abstract

Background

Deterioration of peroxisomal β-oxidation activity causes an accumulation of very long chain saturated fatty acids (VLCSFA) in various organs. We have recently reported that the levels of VLCSFA in the plasma and/or membranes of blood cells were significantly higher in patients with metabolic syndrome and in patients with coronary artery disease than the controls. The aim of the present study is to investigate the effect of VLCSFA accumulation on inflammatory and oxidative responses in VLCSFA-accumulated macrophages derived from X-linked adrenoleukodystrophy (X-ALD) protein (ALDP)-deficient mice.

Results

Elevated levels of VLCSFA were confirmed in macrophages from ALDP-deficient mice. The levels of nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ), intracellular reactive oxygen species (ROS), and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interluekin-6 (IL-6), and interleukin-12p70 (IL-12p70), were significantly higher in macrophages from ALDP-deficient mice than in those from wild-type mice. The inducible NO synthase (iNOS) mRNA expression also showed an increase in macrophages from ALDP-deficient mice.

Conclusion

These results suggested that VLCSFA accumulation in macrophages may contribute to the pathogenesis of inflammatory diseases through the enhancement of inflammatory and oxidative responses.