Department of Drug Science and Technology, University of Turin, 10126 Torino, Italy.
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy.
Sci Rep. 2017 Mar 9;7:43718. 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.
骨桥蛋白是一种多效细胞因子，参与多种疾病，包括多发性硬化症。分泌的骨桥蛋白被少数已知的蛋白酶切割，从而调节其促炎活性。在这里，我们通过体外实验表明，分泌的骨桥蛋白可以被细胞外蛋白酶体处理，从而产生具有新趋化活性的片段。此外，骨桥蛋白减少了细胞外空间中蛋白酶体的释放。后一种现象似乎在多发性硬化症中发生，这反映了缓解/复发交替。细胞外蛋白酶体介导的炎症途径可能代表一种控制炎症性疾病炎症的一般机制。
