Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo
Joint Authors
Dianzani, Chiara
Comi, Cristoforo
Clemente, Nausicaa
Raineri, Davide
Boggio, Elena
Soluri, Maria Felicia
Dianzani, Umberto
Chiocchetti, Annalisa
Gigliotti, Casimiro Luca
Toth, Erika
Ferrara, Benedetta
Cappellano, Giuseppe
Source
Journal of Immunology Research
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-07-13
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Osteopontin is a proinflammatory cytokine and plays a pathogenetic role in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), by recruiting autoreactive T cells into the central nervous system.
Osteopontin functions are modulated by thrombin cleavage generating N- and C-terminal fragment, whose individual roles are only partly known.
Published data are difficult to compare since they have been obtained with heterogeneous approaches.
Interestingly, thrombin cleavage of osteopontin unmasks a cryptic domain of interaction with α 4 β 1 integrin that is the main adhesion molecule involved in lymphocyte transmigration to the brain and is the target for natalizumab, the most potent drug preventing relapses.
We produced recombinant osteopontin and its N- and C-terminal fragments in an eukaryotic system in order to allow their posttranslational modifications.
We investigated, in vitro, their effect on human cells and in vivo in EAE.
We found that the osteopontin cleavage plays a key role in the function of this cytokine and that the two fragments exert distinct effects both in vitro and in vivo.
These findings suggest that drugs targeting each fragment may be used to fine-tune the pathological effects of osteopontin in several diseases.
American Psychological Association (APA)
Boggio, Elena& Dianzani, Chiara& Gigliotti, Casimiro Luca& Soluri, Maria Felicia& Clemente, Nausicaa& Cappellano, Giuseppe…[et al.]. 2016. Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo. Journal of Immunology Research،Vol. 2016, no. 2016, pp.1-13.
https://search.emarefa.net/detail/BIM-1108915
Modern Language Association (MLA)
Boggio, Elena…[et al.]. Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo. Journal of Immunology Research No. 2016 (2016), pp.1-13.
https://search.emarefa.net/detail/BIM-1108915
American Medical Association (AMA)
Boggio, Elena& Dianzani, Chiara& Gigliotti, Casimiro Luca& Soluri, Maria Felicia& Clemente, Nausicaa& Cappellano, Giuseppe…[et al.]. Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo. Journal of Immunology Research. 2016. Vol. 2016, no. 2016, pp.1-13.
https://search.emarefa.net/detail/BIM-1108915
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1108915