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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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Detalles Bibliográficos
Autores principales: Torres, Lidiane S., Chweih, Hanan, Fabris, Fernanda C. Z., Gotardo, Erica M. F., Leonardo, Flávia C., Saad, Sara T. Olalla, Costa, Fernando F., Conran, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998040/
https://www.ncbi.nlm.nih.gov/pubmed/35406764
http://dx.doi.org/10.3390/cells11071200
Descripción
Sumario: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.