Exogenous ghrelin modulates release of pro-inflammatory and anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways.
Surgery
; 143(3): 334-42, 2008 Mar.
Article
em En
| MEDLINE
| ID: mdl-18291254
ABSTRACT
BACKGROUND:
Ghrelin, an orexigenic 28-amino-acid peptide, has been studied primarily in relation to the control of appetite and fat metabolism. In addition to these well-known functions, ghrelin, and its target receptors, growth hormone secretagogue receptors (GHS-Rs), have been localized to neutrophils, lymphocytes, and macrophages, which suggests that ghrelin may be involved in immune modulation.METHODS:
To assess the therapeutic role of ghrelin in production of pro-inflammatory and anti-inflammatory cytokines, the effects of exogenous ghrelin administration on the regulation of cytokine release in lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophages were analyzed.RESULTS:
Ghrelin and GHS-Rs are expressed in murine macrophages. In addition, exogenous ghrelin inhibited the production of pro-inflammatory cytokines IL-1beta and TNF-alpha in LPS-stimulated murine macrophages in a dose dependent and time-dependent fashion. Exogenous ghrelin pretreatment resulted in a decrease in LPS-induced NFkappaB activation and was presumably the reason for this ghrelin-mediated effect. In contrast to these findings, exogenous ghrelin significantly augmented the release of the anti-inflammatory cytokine IL-10 in a dose-dependent and time-dependent fashion from LPS-stimulated murine macrophages. Ghrelin administration enhanced activation of p38 MAPK, which is known to control the release of IL-10 in macrophages independent of the NFkappaB pathway. These effects of ghrelin on both pro-inflammatory and anti-inflammatory cytokines were offset when a specific GHS-R receptor antagonist was added to the culture media.CONCLUSIONS:
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.
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Base de dados:
MEDLINE
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Transdução de Sinais
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Citocinas
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Grelina
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Macrófagos
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article