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

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

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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.

Original languageEnglish
Article number48
JournalLipids in Health and Disease
Volume7
DOIs
Publication statusPublished - 2008

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Fingerprint Dive into the research topics of 'Enhanced production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in very long chain saturated fatty acid-accumulated macrophages'. Together they form a unique fingerprint.

Cite this