Anti-Inflammatory Activity of Ghrelin in Human Carotid Artery Cells
- PDF / 142,308 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 79 Downloads / 204 Views
Anti-Inflammatory Activity of Ghrelin in Human Carotid Artery Cells Kevin B. S. Chow,1 Christopher H. K. Cheng,1 and Helen Wise1,2
Abstract—Receptors for eicosanoids such as prostaglandin E2, prostacyclin and thromboxane A2, as well as the ghrelin receptor polypeptide (GHS-R1b), can all regulate ghrelin (GHS-R1a) receptor activity, by the process of hetero-oligomerization, when heterologously expressed in human embryonic kidney (HEK 293) cells. To determine if such regulation might occur in inflammatory diseases of the vasculature, we incubated human coronary artery endothelial cells and human coronary artery smooth muscle cells with lipopolysaccharide and determined mRNA expression levels of these proteins using real-time PCR. Acute inflammation increased GHS-R1a mRNA in smooth muscle cells and increased cyclo-oxygenase-2 mRNA in endothelial cells; both these changes were attenuated by pretreatment of cells with ghrelin. Lipopolysaccharide did not affect expression of GHS-R1b or prostanoid receptor mRNA. Therefore, hetero-oligomerization of GHS-R1a with GHSR1b or prostanoid receptors is unlikely to influence GHS-R1a activity in the vasculature; at least under conditions of acute vascular inflammation. KEY WORDS: Human coronary artery; ghrelin; inflammation; prostanoid receptors.
negative activity of the truncated ghrelin receptor polypeptide (GHS-R1b) [7]. In addition, we have shown that cell surface expression of ghrelin receptors is also affected by co-transfection of human embryonic kidney (HEK 293) cells with the prostacyclin (IP) receptor, the prostaglandin E2 (PGE2) receptor (EP3-I) subtype, and the thromboxane A2 (TPα) receptor [8]. These prostanoid receptors are also vasoactive and can modulate inflammatory responses [9, 10]. Importantly, ghrelin receptors and these prostanoid receptors are all associated with atherosclerotic plaques [4, 11]. A lack of IP receptors or a decrease in prostacyclin production produces a prothrombotic state [12] allowing for a dominant role for TP receptors [13]. In addition to TP receptors, EP3 receptors are also vasoconstrictors [14] and can stimulate platelet aggregation [15]. The ghrelin receptor shows a high degree of agonist-independent activity in cell-based assays [7]. Therefore, because GHS-R1b, EP3-I, IP and/or TP receptors can decrease the cell surface expression of GHS-R1a [8], they might be expected to decrease both constitutive and agonist-dependent activity and thus
INTRODUCTION There is increasing evidence to show that the appetite-regulating hormone ghrelin [1] additionally behaves as an endothelium-independent vasorelaxant peptide [2] and can display anti-inflammatory actions within the immune system [3]. Ghrelin receptor (GHSR1a) expression is increased in atherosclerotic coronary artery [4], and ghrelin may thus have the therapeutic potential to correct endothelial dysfunction associated with atherosclerosis and metabolic syndrome in a GHSR1a-dependent manner [5, 6]. GHS-R1a is a G protein-coupled receptor whose cell surface expression can be modulated by the domin
Data Loading...
