Exogenous ghrelin modulates release of pro-inflammatory and anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways

Abstract

These data suggest that ghrelin has potent anti-inflammatory properties through modulation of secretion of both pro-inflammatory and anti-inflammatory cytokines from LPS-stimulated macrophages through distinct signaling cascades. Therapeutic utility of ghrelin to control, modulate, or treat pathologic inflammatory conditions like endotoxemic shock and ulcerative colitis requires additional investigation.

Effect of acute and regular exercise on growth hormone secretagogue receptor-1a expression in human lymphocytes, T cell subpopulation and monocytes

“…In the present study circulating concentrations of acylated ghrelin fell to ~40 pg.ml -1 (0.04 ng.ml -1 ) after acute exercise. In vitro inhibition of T cell and monocyte cytokine production via ligation with GHS-R1a is reported at concentrations ranging from 1-1000 ng.ml -1 (Dixit et al, 2004;Waseem et al, 2008). The effect of acylated ghrelin at concentrations of less than 1 ng.ml -1…”

“…Aside from these well-studied effects, ghrelin is now known to play a key role in the regulation of inflammation, with reports of inhibitory effects of the acylated (but not des-acylated) isoform of ghrelin on IL-1β, IL-6 and TNF-α mRNA and protein expression in both human and rodent T cells and monocytes in vivo and in vitro (Dixit et al, 2004;DeBoer et al, 2008;Waseem et al, 2008). Acylated ghrelin also attenuates leptininduced pro-inflammatory cytokine responses in human monocytes and T cells (Dixit et al, 2004).…”

Ghrelin Gene Products in Acute and Chronic Inflammation

“…The effect of ghrelin on pro-inflammatory cytokines induction and release has been related, in several studies, to a suppression of the expression and/or activity of the transcription factor NF-jB (Barazzoni et al 2014;Hou et al 2009;Konturek et al 2006;Li et al 2004;Liu et al 2010;Peng et al 2012;Slomiany and Slomiany 2013;Wang et al 2012;Waseem et al 2008;Wu et al 2005;Yuan et al 2009;Zhou and Xue 2009). However, it has been proposed that in some circumstances and with some cell types, ghrelin may act as a pro-inflammatory peptide inducing, rather than reducing, NF-jB expression and proinflammatory IL-8 secretion (Kwan et al 2010;Rezaeian et al 2012;Sung et al 2011;Zhao et al 2006).…”

Clinical application of ghrelin administration for gastric cancer patients undergoing gastrectomy

“…GH regulates IGF-I levels, promotes anabolism, and increases muscle strength. Ghrelin enhances lipolysis via GH and stimulates protein synthesis, myoblast differentiation, and muscle growth via IGF-1 Antiinflammatory action [20,63,64] Ghrelin inhibits the activation of NF-jB, a transcription factor known to control the production of multiple proinflammatory cytokines during inflammatory insults Stimulation of gastrointestinal peristalsis [18] Ghrelin acts on motor neurons in the myenteric plexus, activates a vago-vagal reflex, or may stimulate central pathways Augmentation of cardiac output and reduction of blood pressure [26] Ghrelin improves myocardial structure and function in chronic heart failure (CHF) via its GH-releasing effects Inhibition of insulin secretion [65,66] Ghrelin has obesogenic/diabetogenic properties. These properties may be direct effects of ghrelin on pancreatic islet function and/or indirect effects through the modulation of GH secretion Application of ghrelin administration 201…”