Open AccessA 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
Author(s) -
Antonio Fèrrante,
B S Robinson,
Harmeet Singh,
Hubertus Jersmann,
Judith Ferrante,
Zhenjun Huang,
Neil A. Trout,
Michael J. Pitt,
Deborah A. Rathjen,
Christopher J. Easton,
A. Poulos,
R. H. Prager,
Frank S. Lee,
Charles S. Hii
Publication year - 2006
Publication title -
circulation research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.899
H-Index - 336
eISSN - 1524-4571
pISSN - 0009-7330
DOI - 10.1161/01.res.0000231292.66084.cd
Subject(s) - cell adhesion molecule , cell adhesion , polyunsaturated fatty acid , microbiology and biotechnology , intercellular adhesion molecule 1 , inflammation , biochemistry , umbilical vein , downregulation and upregulation , chemistry , biology , tumor necrosis factor alpha , immunology , fatty acid , cell , in vitro , gene
Several novel polyunsaturated fatty acids (PUFAs) that contain either an oxygen or sulfur atom in the beta-position were found to exhibit more selective antiinflammatory properties than their natural PUFA counterparts. One of these, beta-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, beta-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 beta-oxa-23:4n-6 required a functional 12- but not 5-lipoxygenase or cyclooxygenases, consistent with its metabolism via the 12-lipoxygenase pathway. Whereas beta-oxa-23:4n-6 did not affect the activation of mitogen-activated protein kinases by tumor necrosis factor, activation of the IkappaB kinase/nuclear factor kappaB pathway was selectively inhibited. These novel PUFAs could form the basis for a potential new class of pharmaceuticals for treating inflammatory diseases, including atherosclerosis.