Article

Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells.

Laboratory of Immunology, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA.
Journal of Clinical Investigation (Impact Factor: 13.77). 08/2004; 114(1):57-66.
Source: PubMed

ABSTRACT Ghrelin, a recently described endogenous ligand for the growth hormone secretagogue receptor (GHS-R), is produced by stomach cells and is a potent circulating orexigen, controlling energy expenditure, adiposity, and growth hormone secretion. However, the functional role of ghrelin in regulation of immune responses remains undefined. Here we report that GHS-R and ghrelin are expressed in human T lymphocytes and monocytes, where ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha. Ghrelin led to a dose-dependent inhibition of leptin-induced cytokine expression, while leptin upregulated GHS-R expression on human T lymphocytes. These data suggest the existence of a reciprocal regulatory network by which ghrelin and leptin control immune cell activation and inflammation. Moreover, ghrelin also exerts potent anti-inflammatory effects and attenuates endotoxin-induced anorexia in a murine endotoxemia model. We believe this to be the first report demonstrating that ghrelin functions as a key signal, coupling the metabolic axis to the immune system, and supporting the potential use of ghrelin and GHS-R agonists in the management of disease-associated cachexia.

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    ABSTRACT: Export Date: 18 October 2014
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    ABSTRACT: Ghrelin and obestatin are two different peptides originated from the same gene isolated in the stomach. Numer-ous actions have been described where these two peptides are implicated in metabolism, appetite regulation, glucose lev-els regulation, and a wide range of systemic effects. In this article, we summarize (1) the cellular receptors implicated in ghrelin and obestatin effects; (2) the role of ghrelin and obestatin in metabolism and appetite regulation; (3) their role in the glucose homeostasis regulation and its implication in diabetes patho-physiology; (5) the effects of ghrelin and obes-tatin in regulation of normal angiogenesis and (6) their possible role in the regulation of diabetes-induced pathologic angi-ogenesis. GHRELIN Ghrelin is an acylated, 28-amino-acid peptide that pro-motes the release of GH in the hypothalamus. It is the natural ligand of the GHSR-1a receptor [1]. For it to act on the GHSR-1a ghrelin has an n-octanoic acid modification on serine 3 residue [2]. The ghrelin gene is located in chromosome 3 (3p25-26) [1], contains four preproghrelin-coding exons, and encodes a precursor of 117aa (preproghrelin) with 82% of homology between species [3]. As a result of alternative splicing of this gene, a 27 aa acylated peptide was identified with the same activity potency as ghrelin (des-Gln14-ghrelin) [4]. Another form of ghrelin, des-acyl ghrelin, exists at significant levels in both stomach and blood. This variant lacks the octanoyl chain in serine 3 and represents more than 90% of the circu-lating peptide [2, 4, 5]. In plasma, acyl ghrelin levels are 10– 20 fmol/ml while total ghrelin levels are 100–150 fmol/ml (including both acyl and non-acyl forms) [6, 7]. Several mi-nor forms of ghrelin were described with modifications on the peptide chain or on the acidic chain and are only present in low amounts [4, 8]. Some of these are independently pro-duced and regulated and their levels are not directly related to those of ghrelin [3]. Finally, in a posttranslational process, this gene can originate a 23 aa peptide named obestatin that has some different and even opposite actions than ghrelin [9].

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