A novel β-oxa polyunsaturated fatty acid downregulates the activation of the IκB kinase/nuclear factor κB pathway, inhibits expression of endothelial cell adhesion molecules, and depresses inflammation

Antonio Ferrante*, Brenton S. Robinson, Harmeet Singh, Hubertus P.A. Jersmann, Judith V. Ferrante, Zhi H. Huang, Neil A. Trout, Michael J. Pitt, Deborah A. Rathjen, Christopher J. Easton, Alf Poulos, Rolf H. Prager, Frank S. Lee, Charles S.T. Hii

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    12 Citations (Scopus)

    Abstract

    Several novel polyunsaturated fatty acids (PUFAs) that contain either an oxygen or sulfur atom in the β-position were found to exhibit more selective antiinflammatory properties than their natural PUFA counterparts. One of these, β-oxa-23:4n-6, unlike natural PUFAs, lacked ability to stimulate oxygen radical production in neutrophils but caused marked inhibition of agonist-induced upregulation of leukocyte adhesion to cultured human umbilical vein endothelial cells (HUVEC) and E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 expression. In addition, β-oxa-23:4n-6 inhibited acute and chronic inflammatory responses in mice as well as the upregulation of adhesion molecule expression in arterial endothelium. This action of β-oxa-23:4n-6 required a functional 12- but not 5-lipoxygenase or cyclooxygenases, consistent with its metabolism via the 12-lipoxygenase pathway. Whereas β-oxa-23:4n-6 did not affect the activation of mitogen-activated protein kinases by tumor necrosis factor, activation of the IκB kinase/nuclear factor κB pathway was selectively inhibited. These novel PUFAs could form the basis for a potential new class of pharmaceuticals for treating inflammatory diseases, including atherosclerosis.

    Original languageEnglish
    Pages (from-to)34-41
    Number of pages8
    JournalCirculation Research
    Volume99
    Issue number1
    DOIs
    Publication statusPublished - Jul 2006

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