title: Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis.
abstract: Osteopontin is a pleiotropic cytokine that is involved in several diseases including multiple sclerosis. Secreted osteopontin is cleaved by few known proteases, modulating its pro-inflammatory activities. Here we show by in vitro experiments that secreted osteopontin can be processed by extracellular proteasomes, thereby producing fragments with novel chemotactic activity. Furthermore, osteopontin reduces the release of proteasomes in the extracellular space. The latter phenomenon seems to occur in vivo in multiple sclerosis, where it reflects the remission/relapse alternation. The extracellular proteasome-mediated inflammatory pathway may represent a general mechanism to control inflammation in inflammatory diseases.
authors.affiliation: Department of Drug Science and Technology, University of Turin, 10126 Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Dianzani
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bellavista
authors.affiliation: Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, SW7 2AZ London, UK.
authors.forename: Juliane
authors.initials: J
authors.lastname: Liepe
authors.affiliation: Institute of Neuroscience, Centro Nazionale delle Ricerche (CNR), 20129 Milano, Italy.|IRCCS Humanitas, 20089 Rozzano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Verderio
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy.
authors.forename: Morena
authors.initials: M
authors.lastname: Martucci
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Amedeo Avogadro, 28100 Novara, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiocchetti
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Amedeo Avogadro, 28100 Novara, Italy.
authors.forename: Casimiro Luca
authors.initials: CL
authors.lastname: Gigliotti
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Amedeo Avogadro, 28100 Novara, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Boggio
authors.affiliation: Department of Drug Science and Technology, University of Turin, 10126 Torino, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Ferrara
authors.affiliation: Institute of Neuroscience, Centro Nazionale delle Ricerche (CNR), 20129 Milano, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Riganti
authors.affiliation: Institut für Biochemie, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.|Berlin Institute of Health, 10117 Berlin, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Keller
authors.affiliation: Institut für Biochemie, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Janek
authors.affiliation: Institut für Biochemie, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Agathe
authors.initials: A
authors.lastname: Niewienda
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, "Dino Ferrari" Centre, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, 20100 Milano, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.affiliation: Department of Neuro-rehabilitation and Laboratory of genetics of Neurological complex disorders, Institute of Experimental Neurology (INSPE) Scientific Institute San Raffaele, 20132 Milano, Italy.
authors.forename: Melissa
authors.initials: M
authors.lastname: Sorosina
authors.affiliation: Department of Translational Medicine, Section of Neurology, University of Piemonte Orientale, 28100 Novara, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cantello
authors.affiliation: Institut für Biochemie, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.|Berlin Institute of Health, 10117 Berlin, Germany.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kloetzel
authors.affiliation: Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, SW7 2AZ London, UK.
authors.forename: Michael P H
authors.initials: MP
authors.lastname: Stumpf
authors.affiliation: AG Klinische Neuroimmunologie des Neurocure Clinical Research Center, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Centre - Universitätsmedizin Berlin, 10117 Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Clinical and Experimental Multiple Sclerosis Research Centre - Universitätsmedizin Berlin, 10117 Berlin, Germany.|Department of Neurology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, "Dino Ferrari" Centre, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, 20100 Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.affiliation: Department of Neuro-rehabilitation and Laboratory of genetics of Neurological complex disorders, Institute of Experimental Neurology (INSPE) Scientific Institute San Raffaele, 20132 Milano, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Martinelli Boneschi
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Amedeo Avogadro, 28100 Novara, Italy.|Department of Translational Medicine, Section of Neurology, University of Piemonte Orientale, 28100 Novara, Italy.
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Comi
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Amedeo Avogadro, 28100 Novara, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Dianzani
authors.affiliation: Institut für Biochemie, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.|Berlin Institute of Health, 10117 Berlin, Germany.|Department of Health Science, University of Piemonte Orientale, 28100 Novara, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Mishto
mesh_terms: D000595:Amino Acid Sequence; D002633:Chemotaxis / Q000276:immunology; D042783:Endothelial Cells / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008958:Models, Molecular; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism*; D053495:Osteopontin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D053495:Osteopontin; D046988:Proteasome Endopeptidase Complex