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PMID:15232612

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Citation

Dixit, VD, Schaffer, EM, Pyle, RS, Collins, GD, Sakthivel, SK, Palaniappan, R, Lillard, JW Jr and Taub, DD (2004) Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J. Clin. Invest. 114:57-66

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.

Links

PubMed PMC437970 Online version:10.1172/JCI21134

Keywords

Cytokines/genetics; Dose-Response Relationship, Drug; Gene Expression Regulation/drug effects; Gene Expression Regulation/immunology; Ghrelin; Human Growth Hormone/pharmacology; Humans; Inflammation; Leptin/antagonists & inhibitors; Leptin/pharmacology; Lymphocyte Activation/drug effects; Monocytes/drug effects; Monocytes/immunology; Peptide Hormones/pharmacology; RNA, Messenger/genetics; Receptors, G-Protein-Coupled/genetics; Receptors, G-Protein-Coupled/immunology; Receptors, G-Protein-Coupled/physiology; Receptors, Ghrelin; Receptors, Leptin; T-Lymphocytes/drug effects; T-Lymphocytes/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:GHSR

involved_in

GO:0032720: negative regulation of tumor necrosis factor production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHSR

involved_in

GO:0032715: negative regulation of interleukin-6 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHSR

located_in

GO:0045121: membrane raft

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000084)

Seeded From UniProt

complete

HUMAN:GHRL

involved_in

GO:0032720: negative regulation of tumor necrosis factor production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHRL

involved_in

GO:0032715: negative regulation of interleukin-6 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHRL

involved_in

GO:0050728: negative regulation of inflammatory response

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHRL

involved_in

GO:0045409: negative regulation of interleukin-6 biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHRL

involved_in

GO:0042536: negative regulation of tumor necrosis factor biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHRL

involved_in

GO:0032691: negative regulation of interleukin-1 beta production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHRL

involved_in

GO:0009725: response to hormone

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHRL

involved_in

GO:0008154: actin polymerization or depolymerization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHSR

involved_in

GO:0008154: actin polymerization or depolymerization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHSR

involved_in

GO:0009725: response to hormone

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHSR

involved_in

GO:0032691: negative regulation of interleukin-1 beta production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHSR

involved_in

GO:0042536: negative regulation of tumor necrosis factor biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHSR

involved_in

GO:0045409: negative regulation of interleukin-6 biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GHSR

part_of

GO:0045121: membrane raft

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000084)

Seeded From UniProt

complete

HUMAN:GHSR

involved_in

GO:0050728: negative regulation of inflammatory response

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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