title: Activation of thromboxane receptor modulates interleukin-1β-induced monocyte adhesion--a novel role of Nox1.
abstract: Activation of thromboxane receptors (TPr) may promote atherosclerosis by enhancing oxidative stress and inflammation. This study examined the role of Nox1, an NADPH-oxidase subunit, in the enhancement of interleukin (IL)-1β-induced monocyte adhesion by TPr. In cultured rat aortic vascular smooth muscle cells (VSMCs), U46619, a stable thromboxane A(2) mimetic, together with interleukin-1β significantly enhanced Nox1 mRNA expression, as well as adhesion of THP-1 monocytes. Activation of TPr also enhanced IL-1β-induced vascular cell adhesion molecule (VCAM)-1 expression, but inhibited inducible nitric oxide synthase (iNOS) expression. Silencing Nox1 expression by siRNA prevented the U46619 enhancement of IL-1β-induced monocyte adhesion, but had no significant effect on VCAM-1 or iNOS expression. Furthermore, monocyte adhesion was inhibited by superoxide dismutase, enhanced by a specific iNOS inhibitor, l-N(6)-(1-iminoethyl)-lysine, but not influenced by catalase. U46619 inhibited IL-1β-induced cyclic GMP production, and the inhibition was partially prevented by superoxide dismutase. In conclusion, activation of TPr enhances IL-1β-induced Nox1 expression in VSMCs, which is responsible for the up-regulation of monocyte adhesion. The effect of Nox1 is independent of the changes in VCAM-1 and iNOS expression, but depends on the inactivation of nitric oxide via generation of superoxide anion.
authors.affiliation: Whitaker Cardiovascular Institute, Vascular Biology Section, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Hossein
authors.initials: H
authors.lastname: Bayat
authors.forename: Katrin
authors.initials: K
authors.lastname: Schröder
authors.forename: David R
authors.initials: DR
authors.lastname: Pimentel
authors.forename: Ralf P
authors.initials: RP
authors.lastname: Brandes
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Verbeuren
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cohen
authors.forename: Bingbing
authors.initials: B
authors.lastname: Jiang
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D017931:DNA Primers; D053583:Interleukin-1beta / Q000502:physiology*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000502:physiology*; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D017482:Receptors, Thromboxane / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D017931:DNA Primers; D053583:Interleukin-1beta; D034741:RNA, Small Interfering; D017482:Receptors, Thromboxane; D019010:Vascular Cell Adhesion Molecule-1; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D052247:Nitric Oxide Synthase Type II; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C000614712:NOX1 protein, rat; C498911:Nox4 protein, rat