title: The neuropeptide galanin modulates natural killer cell function.
abstract: Natural killer (NK) cells are part of the innate immune system and combat pathogens and tumors by secreting pro-inflammatory cytokines like interferon gamma (IFN-γ) and by their cytotoxic action. Galanin is a neuropeptide also expressed in peripheral tissue where it impacts several physiological functions, including inflammation. The effects of galanin are mediated via three receptors, GAL1-3. Since other neuropeptides have been shown to regulate NK cell activity, we investigated the potential of galanin to modulate human NK cell function. NK cells were isolated from human peripheral blood mononuclear cells. mRNA expression was analyzed by qRT-PCR. The dynamic mass redistribution of NK cells upon regulatory peptide stimulation was determined by label-free biochip technology. IFN-γ producing NK cells were identified by flow cytometry analysis and IFN-γ secretion was measured by ELISA. NK cell cytotoxicity was analyzed by flow cytometry via CD107a mobilization. NK cells were found to express the receptor GAL2but not GAL1, GAL3or galanin. Galanin per se did not affect the dynamic mass redistribution of NK cells, but significantly enhanced the response of NK cells to IL-18. Galanin significantly modulated the IFN-γ production of the CD56brightNK cell population upon IL-12 and IL-18 stimulation. Furthermore, galanin significantly modulated the IL-12 and IL-18 stimulated IFN-γ secretion. NK cell cytotoxicity was not modulated by galanin treatment. Galanin can be classified as an immunomodulatory peptide as it is able to sensitize NK cells toward specific cytokines.
authors.affiliation: Laura Bassi Centre of Expertise THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Koller
authors.affiliation: Laura Bassi Centre of Expertise THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Bianchini
authors.affiliation: Department of Blood Group Serology and Transfusion Medicine, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schlager
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Rämistraße 71, 8006 Zürich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
authors.affiliation: Laura Bassi Centre of Expertise THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria. Electronic address: B.Kofler@salk.at.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
authors.affiliation: Department of Neonatology, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria.
authors.forename: Silke
authors.initials: S
authors.lastname: Wiesmayr
mesh_terms: D019004:Galanin / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*
chemical_list: C000589760:IL18 protein, human; D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma; D019004:Galanin
keywords: Galanin; Immunomodulation; Interferon gamma; Interleukin 12; Interleukin 18; Natural killer cells