TGF-β1 Reduces Neutrophil Adhesion and Prevents Acute Vaso-Occlusive Processes in Sickle Cell Disease Mice
Sickle cell disease (SCD) patients experience chronic inflammation and recurrent vaso-occlusive episodes during their entire lifetime. Inflammation in SCD occurs with the overexpression of several inflammatory mediators, including transforming growth factor beta-1 (TGF-β1), a major immune regulator....
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MDPI AG
2022-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/7/1200 |
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| author | Lidiane S. Torres Hanan Chweih Fernanda C. Z. Fabris Erica M. F. Gotardo Flávia C. Leonardo Sara T. Olalla Saad Fernando F. Costa Nicola Conran |
| author_facet | Lidiane S. Torres Hanan Chweih Fernanda C. Z. Fabris Erica M. F. Gotardo Flávia C. Leonardo Sara T. Olalla Saad Fernando F. Costa Nicola Conran |
| author_sort | Lidiane S. Torres |
| collection | DOAJ |
| description | Sickle cell disease (SCD) patients experience chronic inflammation and recurrent vaso-occlusive episodes during their entire lifetime. Inflammation in SCD occurs with the overexpression of several inflammatory mediators, including transforming growth factor beta-1 (TGF-β1), a major immune regulator. In this study, we aimed to investigate the role played by TGF-β1 in vascular inflammation and vaso-occlusion in an animal model of SCD. Using intravital microscopy, we found that a daily dose of recombinant TGF-β1 administration for three consecutive days significantly reduced TNFα-induced leukocyte rolling, adhesion, and extravasation in the microcirculation of SCD mice. In contrast, immunological neutralization of TGF-β, in the absence of inflammatory stimulus, considerably increased these parameters. Our results indicate, for the first time, that TGF-β1 may play a significant ameliorative role in vascular SCD pathophysiology, modulating inflammation and vaso-occlusion. The mechanisms by which TGF-β1 exerts its anti-inflammatory effects in SCD, however, remains unclear. Our in vitro adhesion assays with TNFα-stimulated human neutrophils suggest that TGF-β1 can reduce the adhesive properties of these cells; however, direct effects of TGF-β1 on the endothelium cannot be ruled out. Further investigation of the wide range of the complex biology of this cytokine in SCD pathophysiology and its potential therapeutical use is needed. |
| first_indexed | 2024-03-09T11:59:36Z |
| format | Article |
| id | doaj.art-75058fefdfdd4aa986285a8c865121fd |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T11:59:36Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-75058fefdfdd4aa986285a8c865121fd2023-11-30T23:04:51ZengMDPI AGCells2073-44092022-04-01117120010.3390/cells11071200TGF-β1 Reduces Neutrophil Adhesion and Prevents Acute Vaso-Occlusive Processes in Sickle Cell Disease MiceLidiane S. Torres0Hanan Chweih1Fernanda C. Z. Fabris2Erica M. F. Gotardo3Flávia C. Leonardo4Sara T. Olalla Saad5Fernando F. Costa6Nicola Conran7Hematology and Transfusion Center, University of Campinas—UNICAMP, Campinas, São Paulo 13083-878, BrazilHematology and Transfusion Center, University of Campinas—UNICAMP, Campinas, São Paulo 13083-878, BrazilHematology and Transfusion Center, University of Campinas—UNICAMP, Campinas, São Paulo 13083-878, BrazilHematology and Transfusion Center, University of Campinas—UNICAMP, Campinas, São Paulo 13083-878, BrazilHematology and Transfusion Center, University of Campinas—UNICAMP, Campinas, São Paulo 13083-878, BrazilHematology and Transfusion Center, University of Campinas—UNICAMP, Campinas, São Paulo 13083-878, BrazilHematology and Transfusion Center, University of Campinas—UNICAMP, Campinas, São Paulo 13083-878, BrazilHematology and Transfusion Center, University of Campinas—UNICAMP, Campinas, São Paulo 13083-878, BrazilSickle cell disease (SCD) patients experience chronic inflammation and recurrent vaso-occlusive episodes during their entire lifetime. Inflammation in SCD occurs with the overexpression of several inflammatory mediators, including transforming growth factor beta-1 (TGF-β1), a major immune regulator. In this study, we aimed to investigate the role played by TGF-β1 in vascular inflammation and vaso-occlusion in an animal model of SCD. Using intravital microscopy, we found that a daily dose of recombinant TGF-β1 administration for three consecutive days significantly reduced TNFα-induced leukocyte rolling, adhesion, and extravasation in the microcirculation of SCD mice. In contrast, immunological neutralization of TGF-β, in the absence of inflammatory stimulus, considerably increased these parameters. Our results indicate, for the first time, that TGF-β1 may play a significant ameliorative role in vascular SCD pathophysiology, modulating inflammation and vaso-occlusion. The mechanisms by which TGF-β1 exerts its anti-inflammatory effects in SCD, however, remains unclear. Our in vitro adhesion assays with TNFα-stimulated human neutrophils suggest that TGF-β1 can reduce the adhesive properties of these cells; however, direct effects of TGF-β1 on the endothelium cannot be ruled out. Further investigation of the wide range of the complex biology of this cytokine in SCD pathophysiology and its potential therapeutical use is needed.https://www.mdpi.com/2073-4409/11/7/1200inflammationvaso-occlusionsickle cell anemianeutrophilsvascular adhesion |
| spellingShingle | Lidiane S. Torres Hanan Chweih Fernanda C. Z. Fabris Erica M. F. Gotardo Flávia C. Leonardo Sara T. Olalla Saad Fernando F. Costa Nicola Conran TGF-β1 Reduces Neutrophil Adhesion and Prevents Acute Vaso-Occlusive Processes in Sickle Cell Disease Mice Cells inflammation vaso-occlusion sickle cell anemia neutrophils vascular adhesion |
| title | TGF-β1 Reduces Neutrophil Adhesion and Prevents Acute Vaso-Occlusive Processes in Sickle Cell Disease Mice |
| title_full | TGF-β1 Reduces Neutrophil Adhesion and Prevents Acute Vaso-Occlusive Processes in Sickle Cell Disease Mice |
| title_fullStr | TGF-β1 Reduces Neutrophil Adhesion and Prevents Acute Vaso-Occlusive Processes in Sickle Cell Disease Mice |
| title_full_unstemmed | TGF-β1 Reduces Neutrophil Adhesion and Prevents Acute Vaso-Occlusive Processes in Sickle Cell Disease Mice |
| title_short | TGF-β1 Reduces Neutrophil Adhesion and Prevents Acute Vaso-Occlusive Processes in Sickle Cell Disease Mice |
| title_sort | tgf β1 reduces neutrophil adhesion and prevents acute vaso occlusive processes in sickle cell disease mice |
| topic | inflammation vaso-occlusion sickle cell anemia neutrophils vascular adhesion |
| url | https://www.mdpi.com/2073-4409/11/7/1200 |
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