Juniperonic Acid Incorporation into the Phospholipids of Murine Macrophage Cells Modulates Pro-Inflammatory Mediator Production

Po Jung Tsai, Wen Cheng Huang, Shao Wei Lin, Sung Nien Chen, Hung Jing Shen, Hsiang Chang, Lu Te Chuang

研究成果: 雜誌貢獻文章

1 引文 斯高帕斯(Scopus)

摘要

Juniperonic acid (JPA; Δ5,11,14,17-20:4), originally identified in certain gymnosperm seeds, is a rare n-3 polyunsaturated fatty acid (PUFA) with lipid-modulating effects on rats and anti-proliferative effects on fibroblast cell proliferation. However, little is known how JPA exerted its immunosuppressive effect. The objective of this study was to investigate whether JPA inhibited the production of inflammatory mediators through the modulation of cellular phospholipid fatty acid compositions. Using standard lipid chemistry techniques in conjunction with argentated column chromatography, high-purity JPA (> 98%) was extracted, isolated, and purified from Biota kernels. When murine RAW264.7 macrophages were incubated with increasing concentrations of JPA, amounts of cellular phospholipid total PUFA, JPA, and Δ7-docosatetraenoic acid (Δ7-DTA; elongation product of JPA) increased in a dose-dependent manner; however, the proportions of total monounsaturated fatty acid (MUFA) and arachidonic acid (AA) decreased. JPA suppressed the production of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and the expression of inducible nitric oxide synthase (iNOS) up to 21, 75, 30, and 44%, respectively. The induction of cyclooxygenase-2 (COX-2) over-expression by JPA could account for the doubling of the PGE 2 level. Furthermore, JPA suppressed the expression of phosphorylated mitogen-activated protein kinases (MAPK). In a separate study using the mouse ear edema model, we demonstrated that JPA also significantly suppressed inflammation, as measured by ear thickness and biopsy weight. The anti-inflammatory properties of JPA could be due, in part, to the incorporation of JPA into cellular phospholipids with subsequent modulation of membrane-mediated MAPK signaling.

原文英語
頁(從 - 到)1200-1214
頁數15
期刊Inflammation
41
發行號4
DOIs
出版狀態已發佈 - 2018 八月 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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