RRC ID 43817
Author Kazama K, Usui T, Okada M, Hara Y, Yamawaki H.
Title Omentin plays an anti-inflammatory role through inhibition of TNF-α-induced superoxide production in vascular smooth muscle cells.
Journal Eur J Pharmacol
Abstract Omentin is a recently identified adipocytokine and its effect in vasculature is largely unknown. Here we examined the effects of omentin on smooth muscle cells (SMCs) inflammatory states. Western blotting was performed to analyze inflammatory signal transduction in cultured SMCs. Phosphorylation of nuclear factor-κB (NF-κB), p38 and JNK, and expression of vascular cell adhesion molecule (VCAM)-1 and cyclooxygenase-2 were not induced by omentin (50-300ng/ml, 20min or 24h). On the other hand, tumor necrosis factor-α (TNF-α; 10ng/ml, 20min)-induced phosphorylation of p38 and JNK was significantly inhibited by omentin pretreatment in a concentration-dependent manner (50-300ng/ml, 30min). TNF-α (24h)-induced expression of VCAM-1 was also significantly inhibited by omentin pretreatment in a concentration-dependent manner. Both inhibitor of p38 (SB203580) and JNK (SP600125) significantly inhibited TNF-α-induced VCAM-1 expression. Omentin (300ng/ml, 30min) inhibited TNF-α (1h)-induced nicotinamide adenine dinucleotide phosphate oxidase activity as determined by lucigenin assay. An antioxidant drug, N-acetyl-l-cysteine significantly inhibited TNF-α-induced phosphorylation of p38 and JNK. Furthermore, omentin (300ng/ml, 30min) significantly inhibited TNF-α (24h)-induced monocytic cells adhesion to SMCs. In rat isolated thoracic aorta, omentin (300ng/ml, 30min) inhibited TNF-α (24h)-induced VCAM-1 expression. The present results demonstrate for the first time that omentin plays an anti-inflammatory role by preventing the TNF-α-induced VCAM-1 expression in SMCs. It is suggested that omentin inhibits TNF-α-induced VCAM-1 expression via preventing the activation of p38 and JNK at least in part through inhibition of superoxide production.
Volume 686(1-3)
Pages 116-23
Published 2012-7-5
DOI 10.1016/j.ejphar.2012.04.033
PII S0014-2999(12)00367-6
PMID 22554771
MeSH Animals Anti-Inflammatory Agents / pharmacology* Aorta, Thoracic / drug effects Aorta, Thoracic / physiology Cell Adhesion / drug effects Cytokines / pharmacology* GPI-Linked Proteins / pharmacology Humans In Vitro Techniques JNK Mitogen-Activated Protein Kinases / immunology Lectins / pharmacology* Male Monocytes / drug effects Monocytes / physiology Muscle, Smooth, Vascular / drug effects* Muscle, Smooth, Vascular / physiology Rats Rats, Wistar Recombinant Proteins / pharmacology Superoxides / immunology* Tumor Necrosis Factor-alpha / immunology* Tumor Necrosis Factor-alpha / pharmacology U937 Cells Vascular Cell Adhesion Molecule-1 / immunology p38 Mitogen-Activated Protein Kinases / immunology
IF 3.263
Times Cited 99
Human and Animal Cells U937