{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:23:38Z","timestamp":1791318218469,"version":"4.3.1"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T00:00:00Z","timestamp":1648857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2017\/14594-0"],"award-info":[{"award-number":["2017\/14594-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2014\/00984- 3"],"award-info":[{"award-number":["2014\/00984- 3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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-\u03b21), a major immune regulator. In this study, we aimed to investigate the role played by TGF-\u03b21 in vascular inflammation and vaso-occlusion in an animal model of SCD. Using intravital microscopy, we found that a daily dose of recombinant TGF-\u03b21 administration for three consecutive days significantly reduced TNF\u03b1-induced leukocyte rolling, adhesion, and extravasation in the microcirculation of SCD mice. In contrast, immunological neutralization of TGF-\u03b2, in the absence of inflammatory stimulus, considerably increased these parameters. Our results indicate, for the first time, that TGF-\u03b21 may play a significant ameliorative role in vascular SCD pathophysiology, modulating inflammation and vaso-occlusion. The mechanisms by which TGF-\u03b21 exerts its anti-inflammatory effects in SCD, however, remains unclear. Our in vitro adhesion assays with TNF\u03b1-stimulated human neutrophils suggest that TGF-\u03b21 can reduce the adhesive properties of these cells; however, direct effects of TGF-\u03b21 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.<\/jats:p>","DOI":"10.3390\/cells11071200","type":"journal-article","created":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T02:59:52Z","timestamp":1648954792000},"page":"1200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["TGF-\u03b21 Reduces Neutrophil Adhesion and Prevents Acute Vaso-Occlusive Processes in Sickle Cell Disease Mice"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4598-1899","authenticated-orcid":false,"given":"Lidiane","family":"Torres","sequence":"first","affiliation":[{"name":"Hematology and Transfusion Center, University of Campinas\u2014UNICAMP, Campinas, S\u00e3o Paulo 13083-878, Brazil"},{"name":"Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA"},{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6358-3579","authenticated-orcid":false,"given":"Hanan","family":"Chweih","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Center, University of Campinas\u2014UNICAMP, Campinas, S\u00e3o Paulo 13083-878, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Fabris","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Center, University of Campinas\u2014UNICAMP, Campinas, S\u00e3o Paulo 13083-878, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Gotardo","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Center, University of Campinas\u2014UNICAMP, Campinas, S\u00e3o Paulo 13083-878, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via","family":"Leonardo","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Center, University of Campinas\u2014UNICAMP, Campinas, S\u00e3o Paulo 13083-878, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0809-8068","authenticated-orcid":false,"given":"Sara","family":"Saad","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Center, University of Campinas\u2014UNICAMP, Campinas, S\u00e3o Paulo 13083-878, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Costa","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Center, University of Campinas\u2014UNICAMP, Campinas, S\u00e3o Paulo 13083-878, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5726-7919","authenticated-orcid":false,"given":"Nicola","family":"Conran","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Center, University of Campinas\u2014UNICAMP, Campinas, S\u00e3o Paulo 13083-878, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1146\/annurev.cb.06.110190.003121","article-title":"The transforming growth factor-beta family","volume":"6","author":"Massague","year":"1990","journal-title":"Annu. 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