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.

Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis

DIANZANI, Chiara
First
;
FERRARA, BENEDETTA;
2017-01-01

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.
2017
7
43718
43729
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343429/pdf/srep43718.pdf
Multidisciplinary
Dianzani, Chiara; Bellavista, Elena; Liepe, Juliane; Verderio, Claudia; Martucci, Morena; Santoro, Aurelia; Chiocchetti, Annalisa; Gigliotti, Casimiro Luca; Boggio, Elena; Ferrara, Benedetta; Riganti, Loredana; Keller, Christin; Janek, Katharina; Niewienda, Agathe; Fenoglio, Chiara; Sorosina, Melissa; Cantello, Roberto; Kloetzel, Peter M.; Stumpf, Michael P.H.; Paul, Friedemann; Ruprecht, Klemens; Galimberti, Daniela; Boneschi, Filippo Martinelli; Comi, Cristoforo; Dianzani, Umberto; Mishto, Michele
File in questo prodotto:
File Dimensione Formato  
srep43718.pdf

Accesso aperto

Tipo di file: PDF EDITORIALE
Dimensione 1.9 MB
Formato Adobe PDF
1.9 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1633829
Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 33
  • ???jsp.display-item.citation.isi??? 27
social impact