title: Lack of Galanin 3 Receptor Aggravates Murine Autoimmune Arthritis.
abstract: Neurogenic inflammation mediated by peptidergic sensory nerves has a crucial impact on the pathogenesis of various joint diseases. Galanin is a regulatory sensory neuropeptide, which has been shown to attenuate neurogenic inflammation, modulate neutrophil activation, and be involved in the development of adjuvant arthritis, but our current understanding about its targets and physiological importance is incomplete. Among the receptors of galanin (GAL1-3), GAL3 has been found to be the most abundantly expressed in the vasculature and on the surface of some immune cells. However, since there are minimal in vivo data on the role of GAL3 in joint diseases, we analyzed its involvement in different inflammatory mechanisms of the K/BxN serum transfer-model of autoimmune arthritis employing GAL 3 gene-deficient mice. After arthritis induction, GAL3 knockouts demonstrated increased clinical disease severity and earlier hindlimb edema than wild types. Vascular hyperpermeability determined by in vivo fluorescence imaging was also elevated compared to the wild-type controls. However, neutrophil accumulation detected by in vivo luminescence imaging or arthritic mechanical hyperalgesia was not altered by the lack of the GAL3 receptor. Our findings suggest that GAL3 has anti-inflammatory properties in joints by inhibiting vascular hyperpermeability and consequent edema formation.
authors.affiliation: Molecular Pharmacology Research Team, Neuroscience Centre and János Szentágothai Research Centre, Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Botz
authors.affiliation: Molecular Pharmacology Research Team, Neuroscience Centre and János Szentágothai Research Centre, Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Kemény
authors.affiliation: Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Muellner Hauptstr. 48, 5020, Salzburg, Austria.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Brunner
authors.affiliation: Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Muellner Hauptstr. 48, 5020, Salzburg, Austria.
authors.forename: Felix
authors.initials: F
authors.lastname: Sternberg
authors.affiliation: Department of Physiology, Semmelweis University School of Medicine and MTA-SE "Lendület" Inflammation Physiology Research Group, Budapest, Hungary.
authors.forename: Janka
authors.initials: J
authors.lastname: Csepregi
authors.affiliation: Department of Physiology, Semmelweis University School of Medicine and MTA-SE "Lendület" Inflammation Physiology Research Group, Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Mócsai
authors.affiliation: Molecular Pharmacology Research Team, Neuroscience Centre and János Szentágothai Research Centre, Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Pintér
authors.affiliation: Departments of Pharmacology and Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, Halifax, NS, Canada.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: McDougall
authors.affiliation: Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Muellner Hauptstr. 48, 5020, Salzburg, Austria. b.kofler@salk.at.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
authors.affiliation: Molecular Pharmacology Research Team, Neuroscience Centre and János Szentágothai Research Centre, Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary.|MTA-PTE NAP B Chronic Pain Research Group, Pécs, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
mesh_terms: D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002199:Capillary Permeability; D004487:Edema / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006614:Hindlimb / Q000473:pathology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D044093:Receptor, Galanin, Type 3 / Q000172:deficiency / Q000235:genetics*
chemical_list: D044093:Receptor, Galanin, Type 3
keywords: Arthritis; Galanin; Inflammation; Myeloperoxidase; Neuropeptide; Plasma leakage