Juniperonic Acid Incorporation into the Phospholipids of Murine Macrophage Cells Modulates Pro-Inflammatory Mediator Pro
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ORIGINAL ARTICLE
Juniperonic Acid Incorporation into the Phospholipids of Murine Macrophage Cells Modulates Pro-Inflammatory Mediator Production Po-Jung Tsai,1,2 Wen-Cheng Huang,1 Shao-Wei Lin,3 Sung-Nien Chen,3 Hung-Jing Shen,1 Hsiang Chang,3 and Lu-Te Chuang 3,4
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 PGE2 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. Abstract—
KEY WORDS: Juniperonic acid (JPA); Arachidonic acid (AA); Prostaglandin E2 (PGE2); Type-2 cyclooxygenase (COX-2); Macrophage. 1
Department of Human Development and Family Studies, National Taiwan Normal University, Taipei, Taiwan 2 Program of Nutritional Science, School of Life Science, National Taiwan Normal University, Taipei, Taiwan 3 Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, 306 Yuanpei Street, Hsinchu, 300, Taiwan 4 To whom correspondence should be addressed at Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, 306 Yuanpei Street, Hsinchu, 300, Taiwan. E-mail: [email protected]
INTRODUCTION Juniperonic acid (JPA; Δ5,11,14,17-20:4), a rare n-3 polyunsaturated fatty acid (PUFA), originally identified in seeds of certain gymnosperm plants, such as Juniperus communis, Biota orientalis, and Ginkgo biloba [1–3]. It is also found in some flowering plants and m
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