title: Omentin, a novel adipocytokine inhibits TNF-induced vascular inflammation in human endothelial cells.
abstract: Omentin is a recently identified adipocytokine with insulin-sensitizing effect. While lack of omentin may be related to the pathogenesis of obesity-related cardiovascular diseases, its effect in vasculature is largely unknown. We examined effects of omentin on vascular endothelial inflammatory states. Western blotting was performed to analyze inflammatory signal transduction in cultured vascular endothelia cells. The cyclic guanosine monophosphate (cGMP) content was measured using enzyme immunoassay. Treatment of human umbilical vein endothelial cells with omentin (300 ng/ml, 20 min) induced phosphorylation of 5'-AMP-activated protein kinase (AMPK) (Thr 172) and endothelial nitric oxide (NO) synthase (eNOS) (Ser 1177). Consistently, omentin increased the cGMP level. Pretreatment with omentin (300 ng/ml, 30 min) significantly inhibited the phosphorylation of JNK as well as expression of cyclooxygenase (COX)-2 by TNF-α (5 ng/ml, 20 min-24h). An inhibitor of JNK significantly inhibited the TNF-α-induced COX-2 expression. Inhibitory effect of omentin on TNF-α-induced COX-2 was reversed by a NOS inhibitor. The present results demonstrate for the first time that omentin plays an anti-inflammatory role by preventing the TNF-α-induced COX-2 expression in vascular endothelial cells. Omentin inhibits COX-2 induction via preventing the JNK activation presumably through activation of AMPK/eNOS/NO pathways.
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan. yamawaki@vmas.kitasato-u.ac.jp
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamawaki
authors.forename: Junji
authors.initials: J
authors.lastname: Kuramoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kameshima
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Usui
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Okada
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hara
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000494:pharmacology / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014657:Vasculitis / Q000378:metabolism*
chemical_list: D054392:Adipokines; D016207:Cytokines; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D037102:Lectins; D014409:Tumor Necrosis Factor-alpha; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2