Fasciola hepatica extract suppresses fibroblast-like synoviocytes in vitro and alleviates experimental arthritis
Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation, fibroblast-like synoviocytes (FLS) activation and joint destruction. Fasciola hepatica is a platyhelminth that releases excretory-secretory immunomodulatory products capable of sup...
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Advances in Rheumatology |
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| Online Access: | https://doi.org/10.1186/s42358-022-00275-y |
| _version_ | 1817970249871392768 |
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| author | Suelen Pizzolatto Dalmolin Renata Ternus Pedó Thales Hein da Rosa Jordana Miranda de Souza Silva Mirian Farinon Maria Luísa Gasparini Eduardo Cremonese Filippi Chiela Ana Helena Paz Martín Pablo Cancela Sehabiague Henrique Bunselmeyer Ferreira Rafaela Cavalheiro do Espírito Santo Fabiany da Costa Gonçalves Ricardo Machado Xavier |
| author_facet | Suelen Pizzolatto Dalmolin Renata Ternus Pedó Thales Hein da Rosa Jordana Miranda de Souza Silva Mirian Farinon Maria Luísa Gasparini Eduardo Cremonese Filippi Chiela Ana Helena Paz Martín Pablo Cancela Sehabiague Henrique Bunselmeyer Ferreira Rafaela Cavalheiro do Espírito Santo Fabiany da Costa Gonçalves Ricardo Machado Xavier |
| author_sort | Suelen Pizzolatto Dalmolin |
| collection | DOAJ |
| description | Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation, fibroblast-like synoviocytes (FLS) activation and joint destruction. Fasciola hepatica is a platyhelminth that releases excretory-secretory immunomodulatory products capable of suppressing the Th1 immune response. Despite the effectiveness of available treatments for inducing disease remission, current options are not successful in all patients and may cause side effects. Thus, we evaluated the therapeutic potential of F. hepatica extract on FLS from RA patients and arthritis models. Methods FLS were isolated from synovial fluid of RA patients, cultured, and exposed to F. hepatica extract (60, 80, and 100 µg/ml) for different time points to assess cell viability, adherence, migration and invasion. For in vivo experiments, mice with antigen (AIA) and collagen (CIA) induced arthritis received a 200 µg/dose of F. hepatica extract daily. Statistical analysis was performed by ANOVA and Student's t-test using GraphPad Prism 6.0. Results In vitro assays showed that extract decreased FLS cell viability at concentration of 100 µg/ml (83.8% ± 5.0 extract vs. 100.0% ± 0.0 control; p < 0.05), adherence in 20% (92.0 cells ± 5.8 extract vs. 116.3 cells ± 7.9 control; p < 0.05), migratory potential (69.5% ± 17.6 extract vs. 100.0% control; p < 0.05), and cell invasiveness potential through the matrigel (76.0% ± 8.4 extract vs. 100.0% control; p < 0.01). The extract reduced leukocyte migration by 56% (40 × 104 leukocytes/knee ± 19.00) compared to control (90.90 × 104 leukocytes/knee ± 12.90) (p < 0.01) and nociception (6.37 g ± 0.99 extract vs. 3.81 g ± 1.44 control; p < 0.001) in AIA and delayed clinical onset of CIA (11.75 ± 2.96 extract vs. 14.00 ± 2.56 control; p = 0.126). Conclusion Our results point out a potential immunomodulatory effect of F. hepatica extract in RA models. Therefore, the characterization of promising new immunomodulatory molecules should be pursued, as they can promote the development of new therapies. Trial registration Collection of synovial liquid and in vitro procedures were approved by the Ethics Committee with Certificate of Presentation of Ethical Appreciation in Plataforma Brasil (CAAE: 89044918.8.0000.5327; date of registration: 26/07/2018). |
| first_indexed | 2024-04-13T20:31:26Z |
| format | Article |
| id | doaj.art-b057801e12464722a005c3799409b6d2 |
| institution | Directory Open Access Journal |
| issn | 2523-3106 |
| language | English |
| last_indexed | 2024-04-13T20:31:26Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Advances in Rheumatology |
| spelling | doaj.art-b057801e12464722a005c3799409b6d22022-12-22T02:31:09ZengBMCAdvances in Rheumatology2523-31062022-11-0162111310.1186/s42358-022-00275-yFasciola hepatica extract suppresses fibroblast-like synoviocytes in vitro and alleviates experimental arthritisSuelen Pizzolatto Dalmolin0Renata Ternus Pedó1Thales Hein da Rosa2Jordana Miranda de Souza Silva3Mirian Farinon4Maria Luísa Gasparini5Eduardo Cremonese Filippi Chiela6Ana Helena Paz7Martín Pablo Cancela Sehabiague8Henrique Bunselmeyer Ferreira9Rafaela Cavalheiro do Espírito Santo10Fabiany da Costa Gonçalves11Ricardo Machado Xavier12Laboratório de Doenças Autoimunes, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto AlegreLaboratório de Doenças Autoimunes, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto AlegreLaboratório de Doenças Autoimunes, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto AlegreLaboratório de Doenças Autoimunes, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto AlegreLaboratório de Doenças Autoimunes, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto AlegreLaboratório de Doenças Autoimunes, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto AlegrePrograma de Pós-Graduação Ciências em Gastroenterologia e Hepatologia, Faculdade de Medicina, Universidade Federal do Rio Grande do SulPrograma de Pós-Graduação Ciências em Gastroenterologia e Hepatologia, Faculdade de Medicina, Universidade Federal do Rio Grande do SulDepartamento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do SulDepartamento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do SulLaboratório de Doenças Autoimunes, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto AlegreDepartment of Internal Medicine, Nephrology and Transplantation, Erasmus Medical CenterLaboratório de Doenças Autoimunes, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto AlegreAbstract Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation, fibroblast-like synoviocytes (FLS) activation and joint destruction. Fasciola hepatica is a platyhelminth that releases excretory-secretory immunomodulatory products capable of suppressing the Th1 immune response. Despite the effectiveness of available treatments for inducing disease remission, current options are not successful in all patients and may cause side effects. Thus, we evaluated the therapeutic potential of F. hepatica extract on FLS from RA patients and arthritis models. Methods FLS were isolated from synovial fluid of RA patients, cultured, and exposed to F. hepatica extract (60, 80, and 100 µg/ml) for different time points to assess cell viability, adherence, migration and invasion. For in vivo experiments, mice with antigen (AIA) and collagen (CIA) induced arthritis received a 200 µg/dose of F. hepatica extract daily. Statistical analysis was performed by ANOVA and Student's t-test using GraphPad Prism 6.0. Results In vitro assays showed that extract decreased FLS cell viability at concentration of 100 µg/ml (83.8% ± 5.0 extract vs. 100.0% ± 0.0 control; p < 0.05), adherence in 20% (92.0 cells ± 5.8 extract vs. 116.3 cells ± 7.9 control; p < 0.05), migratory potential (69.5% ± 17.6 extract vs. 100.0% control; p < 0.05), and cell invasiveness potential through the matrigel (76.0% ± 8.4 extract vs. 100.0% control; p < 0.01). The extract reduced leukocyte migration by 56% (40 × 104 leukocytes/knee ± 19.00) compared to control (90.90 × 104 leukocytes/knee ± 12.90) (p < 0.01) and nociception (6.37 g ± 0.99 extract vs. 3.81 g ± 1.44 control; p < 0.001) in AIA and delayed clinical onset of CIA (11.75 ± 2.96 extract vs. 14.00 ± 2.56 control; p = 0.126). Conclusion Our results point out a potential immunomodulatory effect of F. hepatica extract in RA models. Therefore, the characterization of promising new immunomodulatory molecules should be pursued, as they can promote the development of new therapies. Trial registration Collection of synovial liquid and in vitro procedures were approved by the Ethics Committee with Certificate of Presentation of Ethical Appreciation in Plataforma Brasil (CAAE: 89044918.8.0000.5327; date of registration: 26/07/2018).https://doi.org/10.1186/s42358-022-00275-yRheumatoid arthritisFibroblast-like synoviocytesAntigen-induced arthritisCollagen-induced arthritisFasciola hepatica |
| spellingShingle | Suelen Pizzolatto Dalmolin Renata Ternus Pedó Thales Hein da Rosa Jordana Miranda de Souza Silva Mirian Farinon Maria Luísa Gasparini Eduardo Cremonese Filippi Chiela Ana Helena Paz Martín Pablo Cancela Sehabiague Henrique Bunselmeyer Ferreira Rafaela Cavalheiro do Espírito Santo Fabiany da Costa Gonçalves Ricardo Machado Xavier Fasciola hepatica extract suppresses fibroblast-like synoviocytes in vitro and alleviates experimental arthritis Advances in Rheumatology Rheumatoid arthritis Fibroblast-like synoviocytes Antigen-induced arthritis Collagen-induced arthritis Fasciola hepatica |
| title | Fasciola hepatica extract suppresses fibroblast-like synoviocytes in vitro and alleviates experimental arthritis |
| title_full | Fasciola hepatica extract suppresses fibroblast-like synoviocytes in vitro and alleviates experimental arthritis |
| title_fullStr | Fasciola hepatica extract suppresses fibroblast-like synoviocytes in vitro and alleviates experimental arthritis |
| title_full_unstemmed | Fasciola hepatica extract suppresses fibroblast-like synoviocytes in vitro and alleviates experimental arthritis |
| title_short | Fasciola hepatica extract suppresses fibroblast-like synoviocytes in vitro and alleviates experimental arthritis |
| title_sort | fasciola hepatica extract suppresses fibroblast like synoviocytes in vitro and alleviates experimental arthritis |
| topic | Rheumatoid arthritis Fibroblast-like synoviocytes Antigen-induced arthritis Collagen-induced arthritis Fasciola hepatica |
| url | https://doi.org/10.1186/s42358-022-00275-y |
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