Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo
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...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2016/9345495 |
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| author | Elena Boggio Chiara Dianzani Casimiro Luca Gigliotti Maria Felicia Soluri Nausicaa Clemente Giuseppe Cappellano Erika Toth Davide Raineri Benedetta Ferrara Cristoforo Comi Umberto Dianzani Annalisa Chiocchetti |
| author_facet | Elena Boggio Chiara Dianzani Casimiro Luca Gigliotti Maria Felicia Soluri Nausicaa Clemente Giuseppe Cappellano Erika Toth Davide Raineri Benedetta Ferrara Cristoforo Comi Umberto Dianzani Annalisa Chiocchetti |
| author_sort | Elena Boggio |
| collection | DOAJ |
| description | 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 α4β1 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. |
| format | Article |
| id | doaj-art-60cf1ac6cece4819805b72bf98721aed |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-60cf1ac6cece4819805b72bf98721aed2025-02-03T01:07:45ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/93454959345495Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In VivoElena Boggio0Chiara Dianzani1Casimiro Luca Gigliotti2Maria Felicia Soluri3Nausicaa Clemente4Giuseppe Cappellano5Erika Toth6Davide Raineri7Benedetta Ferrara8Cristoforo Comi9Umberto Dianzani10Annalisa Chiocchetti11Department of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), “A. Avogadro” University of Piemonte Orientale (UPO), 28100 Novara, ItalyDepartment of Drug Science and Technology, University of Torino, 10125 Torino, ItalyDepartment of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), “A. Avogadro” University of Piemonte Orientale (UPO), 28100 Novara, ItalyDepartment of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), “A. Avogadro” University of Piemonte Orientale (UPO), 28100 Novara, ItalyDepartment of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), “A. Avogadro” University of Piemonte Orientale (UPO), 28100 Novara, ItalyBiocenter, Division for Experimental Pathophysiology and Immunology, Laboratory of Autoimmunity, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), “A. Avogadro” University of Piemonte Orientale (UPO), 28100 Novara, ItalyDepartment of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), “A. Avogadro” University of Piemonte Orientale (UPO), 28100 Novara, ItalyDepartment of Drug Science and Technology, University of Torino, 10125 Torino, ItalyDepartment of Translational Medicine, Neurology Unit, “A. Avogadro” UPO, 28100 Novara, ItalyDepartment of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), “A. Avogadro” University of Piemonte Orientale (UPO), 28100 Novara, ItalyDepartment of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), “A. Avogadro” University of Piemonte Orientale (UPO), 28100 Novara, ItalyOsteopontin 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 α4β1 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.http://dx.doi.org/10.1155/2016/9345495 |
| spellingShingle | Elena Boggio Chiara Dianzani Casimiro Luca Gigliotti Maria Felicia Soluri Nausicaa Clemente Giuseppe Cappellano Erika Toth Davide Raineri Benedetta Ferrara Cristoforo Comi Umberto Dianzani Annalisa Chiocchetti Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo Journal of Immunology Research |
| title | Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo |
| title_full | Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo |
| title_fullStr | Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo |
| title_full_unstemmed | Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo |
| title_short | Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo |
| title_sort | thrombin cleavage of osteopontin modulates its activities in human cells in vitro and mouse experimental autoimmune encephalomyelitis in vivo |
| url | http://dx.doi.org/10.1155/2016/9345495 |
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