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

作者：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

来源：Scientific Reports, 2017, 7(1): 43718.

DOI：10.1038/srep43718

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.

• 出版日期2017-3-9