Ghrelin inhibits proinflammatory responses and nuclear factor-kappaB activation in human endothelial cells. Circulation 2004 May 11;109(18):2221-6
Date
05/01/2004Pubmed ID
15117840DOI
10.1161/01.CIR.0000127956.43874.F2Scopus ID
2-s2.0-2442419837 (requires institutional sign-in at Scopus site) 490 CitationsAbstract
BACKGROUND: Ghrelin is a novel growth hormone-releasing peptide that has been shown to improve cachexia in heart failure and cancer and to ameliorate the hemodynamic and metabolic disturbances in septic shock. Because cytokine-induced inflammation is critical in these pathological states and because the growth hormone secretagogue receptor has been identified in blood vessels, we examined whether ghrelin inhibits proinflammatory responses in human endothelial cells in vitro and after administration of endotoxin to rats in vivo.
METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were treated with or without tumor necrosis factor-alpha (TNF-alpha), and induction of proinflammatory cytokines and mononuclear cell adhesion were determined. Ghrelin (0.1 to 1000 ng/mL) inhibited both basal and TNF-alpha-induced cytokine release and mononuclear cell binding. Intravenous administration of ghrelin also inhibited endotoxin-induced proinflammatory cytokine production in rats in vivo. Ghrelin inhibited H2O2-induced cytokine release in HUVECs, suggesting that the peptide blocks redox-mediated cellular signaling. Moreover, ghrelin inhibited basal and TNF-alpha-induced activation of nuclear factor-kappaB. Des-acyl ghrelin had no effect on TNF-alpha-induced cytokine production in HUVECs, suggesting that the antiinflammatory effects of ghrelin require interaction with endothelial growth hormone secretagogue receptors.
CONCLUSIONS: Ghrelin inhibits proinflammatory cytokine production, mononuclear cell binding, and nuclear factor-kappaB activation in human endothelial cells in vitro and endotoxin-induced cytokine production in vivo. These novel antiinflammatory actions of ghrelin suggest that the peptide could play a modulatory role in atherosclerosis, especially in obese patients, in whom ghrelin levels are reduced.
Author List
Li WG, Gavrila D, Liu X, Wang L, Gunnlaugsson S, Stoll LL, McCormick ML, Sigmund CD, Tang C, Weintraub NLAuthor
Curt D. Sigmund PhD Chair, Interim Center Director, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnti-Inflammatory Agents, Non-Steroidal
Arteriosclerosis
Cell Adhesion
Cells, Cultured
Chemokine CCL2
Depression, Chemical
Endothelial Cells
Endothelium, Vascular
Endotoxemia
Gene Expression Regulation
Genes, Reporter
Ghrelin
Humans
Hydrogen Peroxide
Interleukin-8
NF-kappa B
Peptide Hormones
Random Allocation
Rats
Rats, Sprague-Dawley
Signal Transduction
Tumor Necrosis Factor-alpha
U937 Cells
Umbilical Veins
