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

Yanagisawa Naotake, Shimada Kazunori, Miyazaki Tetsuro, Kume Atsumi, Kitamura Yohei, Sumiyoshi Katsuhiko, Kiyanagi Takashi, Iesaki Takafumi, Inoue Nao, Daida, Daida Hiroyuki

Description

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.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2008
• Nombre de lectures: 9
• Langue: English

Extrait

Lipids in Health and Disease

BioMedCentral

Open Access Research Enhanced production of nitric oxide, reactive oxygen species, and proinflammatory cytokines in very long chain saturated fatty acidaccumulated macrophages 1,2 1 1 Naotake Yanagisawa , Kazunori Shimada* , Tetsuro Miyazaki , 1 2 1 1 Atsumi Kume , Yohei Kitamura , Katsuhiko Sumiyoshi , Takashi Kiyanagi , 3 1 1 Takafumi Iesaki , Nao Inoue and Hiroyuki Daida

1 2 Address: Department of Cardiovascular Medicine, Juntendo University School of Medicine, Tokyo, Japan, Nutritional Science Institute, Morinaga 3 Milk Industry Co., Ltd., Kanagawa, Japan and Department of Organ and Cell Physiology, Juntendo University School of Medicine, Tokyo, Japan

Email: Naotake Yanagisawa  n[e-mail]; Kazunori Shimada*  [e-mail]; Tetsuro Miyazaki  [e-mail]; Atsumi Kume  [e-mail]; Yohei Kitamura  yo[e-mail]; Katsuhiko Sumiyoshi  [e-mail]; Takashi Kiyanagi  [e-mail]; Takafumi Iesaki  [e-mail]; Nao Inoue  [e-mail]; Hiroyuki Daida  [e-mail] * Corresponding author

Published: 28 November 2008 Received: 10 October 2008 Accepted: 28 November 2008 Lipids in Health and Disease2008,7:48 doi:10.1186/1476511X748 This article is available from: http://www.lipidworld.com/content/7/1/48 © 2008 Yanagisawa et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background:Deterioration of peroxisomalβ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.

Background Deterioration in peroxisomalβoxidation activity plays a critical role in ageing and inflammatoryrelated disorders

through the accumulation of very long chain saturated fatty acids (VLCSFA) in various organs [1,2]. VLCSFA with more than 22 carbon atoms are almost exclusively oxi

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