title: Ghrelin augments murine T-cell proliferation by activation of the phosphatidylinositol-3-kinase, extracellular signal-regulated kinase and protein kinase C signaling pathways.
abstract: Thymic atrophy occurs during normal aging, and is accelerated by exposure to chronic stressors that elevate glucocorticoid levels and impair the naïve T cell output. The orexigenic hormone ghrelin was recently shown to attenuate age-associated thymic atrophy. Here, we report that ghrelin enhances the proliferation of murine CD4+ primary T cells and a CD4+ T-cell line. Ghrelin induced activation of the ERK1/2 and Akt signaling pathways, via upstream activation of phosphatidylinositol-3-kinase and protein kinase C, to enhance T-cell proliferation. Moreover, ghrelin induced expression of the cell cycle proteins cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2) and retinoblastoma phosphorylation. Finally, ghrelin activated the above-mentioned signaling pathways and stimulated thymocyte proliferation in young and older mice in vivo.
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States; Department of Biochemistry and Division of Brain Korea 21 Plus Program for Biomedical Science, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States.
authors.forename: Kalpesh
authors.initials: K
authors.lastname: Patel
authors.affiliation: Laboratory of Cardiovascular Science, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Tae
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States.
authors.forename: Ana
authors.initials: A
authors.lastname: Lustig
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States.
authors.forename: Jie Wan
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States. Electronic address: mark.mattson@nih.gov.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States; Center of Translational Studies, Medical Services, Veteran Affairs Medical Center, Washington, DC 20422, United States. Electronic address: Daniel.Taub@va.gov.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Taub
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D003907:Dexamethasone; D048049:Extracellular Signal-Regulated MAP Kinases; D054439:Ghrelin; D058539:Phosphatidylinositol 3-Kinase; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D011948:Receptors, Antigen, T-Cell; D054440:Receptors, Ghrelin; C000592182:Ghsr protein, Mouse
keywords: Ghrelin; Glucocorticoid; Proliferation; Signaling; Stress; T-cell; Thymus