Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in mice
Abstract Background Anti-Tumor Necrosis Factor-alpha therapy has become clinically important for treating inflammatory bowel disease. However, the use of conventional immunotherapy requires a systemic exposure of patients and collateral side effects. Lactic acid bacteria have been shown to be effect...
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| Format: | Article |
| Language: | English |
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BMC
2019-06-01
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| Series: | BMC Biotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12896-019-0518-6 |
| _version_ | 1818291666165956608 |
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| author | Maria José Chiabai Juliana Franco Almeida Mariana Gabriela Dantas de Azevedo Suelen Soares Fernandes Vanessa Bastos Pereira Raffael Júnio Araújo de Castro Márcio Sousa Jerônimo Isabel Garcia Sousa Leonora Maciel de Souza Vianna Anderson Miyoshi Anamelia Lorenzetti Bocca Andrea Queiroz Maranhão Marcelo Macedo Brigido |
| author_facet | Maria José Chiabai Juliana Franco Almeida Mariana Gabriela Dantas de Azevedo Suelen Soares Fernandes Vanessa Bastos Pereira Raffael Júnio Araújo de Castro Márcio Sousa Jerônimo Isabel Garcia Sousa Leonora Maciel de Souza Vianna Anderson Miyoshi Anamelia Lorenzetti Bocca Andrea Queiroz Maranhão Marcelo Macedo Brigido |
| author_sort | Maria José Chiabai |
| collection | DOAJ |
| description | Abstract Background Anti-Tumor Necrosis Factor-alpha therapy has become clinically important for treating inflammatory bowel disease. However, the use of conventional immunotherapy requires a systemic exposure of patients and collateral side effects. Lactic acid bacteria have been shown to be effective as mucosal delivering system for cytokine and single domain antibodies, and it is amenable to clinical purposes. Therefore, lactic acid bacteria may function as vehicles for delivery of therapeutic antibodies molecules to the gastrointestinal tract restricting the pharmacological effect towards the gut. Here, we use the mucosal delivery of Lactococcus lactis carrying an anti-TNFα scFv expression plasmid on a DSS-induced colitis model in mice. Results Experimental colitis was induced with DSS administered in drinking water. L. lactis carrying the scFv expression vector was introduced by gavage. After four days of treatment, animals showed a significant improvement in histological score and disease activity index compared to those of untreated animals. Moreover, treated mice display IL-6, IL17A, IL1β, IL10 and FOXP3 mRNA levels similar to health control mice. Therefore, morphological and molecular markers suggest amelioration of the experimentally induced colitis. Conclusion These results provide evidence for the use of this alternative system for delivering therapeutic biopharmaceuticals in loco for treating inflammatory bowel disease, paving the way for a novel low-cost and site-specific biotechnological route for the treatment of inflammatory disorders. |
| first_indexed | 2024-12-13T02:47:41Z |
| format | Article |
| id | doaj.art-0ec68aed5e3847a9b7f0506a0a7468e0 |
| institution | Directory Open Access Journal |
| issn | 1472-6750 |
| language | English |
| last_indexed | 2024-12-13T02:47:41Z |
| publishDate | 2019-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biotechnology |
| spelling | doaj.art-0ec68aed5e3847a9b7f0506a0a7468e02022-12-22T00:02:08ZengBMCBMC Biotechnology1472-67502019-06-0119111210.1186/s12896-019-0518-6Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in miceMaria José Chiabai0Juliana Franco Almeida1Mariana Gabriela Dantas de Azevedo2Suelen Soares Fernandes3Vanessa Bastos Pereira4Raffael Júnio Araújo de Castro5Márcio Sousa Jerônimo6Isabel Garcia Sousa7Leonora Maciel de Souza Vianna8Anderson Miyoshi9Anamelia Lorenzetti Bocca10Andrea Queiroz Maranhão11Marcelo Macedo Brigido12Laboratório de Imunologia Molecular, Departamento de Biologia Molecular, Universidade de BrasíliaCentro de Biotecnologia, Departamento de Biologia Celular e Molecular, Universidade Federal da ParaíbaLaboratório de Imunologia Molecular, Departamento de Biologia Molecular, Universidade de BrasíliaLaboratório de Imunologia Molecular, Departamento de Biologia Molecular, Universidade de BrasíliaLaboratório de Tecnologia Genética, Departamento de Biologia Geral, Universidade Federal de Minas GeraisLaboratório de Imunologia Aplicada, Departamento de Biologia Celular, Universidade de BrasíliaLaboratório de Imunologia Aplicada, Departamento de Biologia Celular, Universidade de BrasíliaLaboratório de Imunologia Molecular, Departamento de Biologia Molecular, Universidade de BrasíliaDepartmento de Patologia, Escola de Medicina, Universidade de BrasíliaLaboratório de Tecnologia Genética, Departamento de Biologia Geral, Universidade Federal de Minas GeraisLaboratório de Imunologia Aplicada, Departamento de Biologia Celular, Universidade de BrasíliaLaboratório de Imunologia Molecular, Departamento de Biologia Molecular, Universidade de BrasíliaLaboratório de Imunologia Molecular, Departamento de Biologia Molecular, Universidade de BrasíliaAbstract Background Anti-Tumor Necrosis Factor-alpha therapy has become clinically important for treating inflammatory bowel disease. However, the use of conventional immunotherapy requires a systemic exposure of patients and collateral side effects. Lactic acid bacteria have been shown to be effective as mucosal delivering system for cytokine and single domain antibodies, and it is amenable to clinical purposes. Therefore, lactic acid bacteria may function as vehicles for delivery of therapeutic antibodies molecules to the gastrointestinal tract restricting the pharmacological effect towards the gut. Here, we use the mucosal delivery of Lactococcus lactis carrying an anti-TNFα scFv expression plasmid on a DSS-induced colitis model in mice. Results Experimental colitis was induced with DSS administered in drinking water. L. lactis carrying the scFv expression vector was introduced by gavage. After four days of treatment, animals showed a significant improvement in histological score and disease activity index compared to those of untreated animals. Moreover, treated mice display IL-6, IL17A, IL1β, IL10 and FOXP3 mRNA levels similar to health control mice. Therefore, morphological and molecular markers suggest amelioration of the experimentally induced colitis. Conclusion These results provide evidence for the use of this alternative system for delivering therapeutic biopharmaceuticals in loco for treating inflammatory bowel disease, paving the way for a novel low-cost and site-specific biotechnological route for the treatment of inflammatory disorders.http://link.springer.com/article/10.1186/s12896-019-0518-6Lactococcus lactisMucosal deliveryAnti-TNFαscFvColitisDSS |
| spellingShingle | Maria José Chiabai Juliana Franco Almeida Mariana Gabriela Dantas de Azevedo Suelen Soares Fernandes Vanessa Bastos Pereira Raffael Júnio Araújo de Castro Márcio Sousa Jerônimo Isabel Garcia Sousa Leonora Maciel de Souza Vianna Anderson Miyoshi Anamelia Lorenzetti Bocca Andrea Queiroz Maranhão Marcelo Macedo Brigido Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in mice BMC Biotechnology Lactococcus lactis Mucosal delivery Anti-TNFα scFv Colitis DSS |
| title | Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in mice |
| title_full | Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in mice |
| title_fullStr | Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in mice |
| title_full_unstemmed | Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in mice |
| title_short | Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in mice |
| title_sort | mucosal delivery of lactococcus lactis carrying an anti tnf scfv expression vector ameliorates experimental colitis in mice |
| topic | Lactococcus lactis Mucosal delivery Anti-TNFα scFv Colitis DSS |
| url | http://link.springer.com/article/10.1186/s12896-019-0518-6 |
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