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PLoS One ; 10(8): e0136116, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26312490

RESUMEN

The transforming growth factor beta 1 (TGF-ß1) is a pleiotropic cytokine with multiple roles in development, wound healing, and immune regulation. TGF-ß1-mediated immune dysfunction may lead to pathological conditions, such as inflammation. Chronic inflammatory process is characterized by a continuous release of pro-inflammatory cytokines, and the inhibition or the blockage of these cytokines signaling pathways are considered a target treatment. In this context, despite the high numbers of TGF-ß-targeted pathways, the inducible regulatory T cells (iTreg) to control inflammation seems to be a promising approach. Our aim was to develop novel peptides through phage display (PhD) technology that could mimic TGF-ß1 function with higher potency. Specific mimetic peptides were obtained through a PhD subtraction strategy from whole cell binding using TGF-ß1 recombinant as a competitor during elution step. We have selected a peptide that seems to play an important role on cellular differentiation and modulation of TNF-α and IL-10 cytokines. The synthetic pm26TGF-ß1 peptide tested in PBMC significantly down-modulated TNF-α and up-regulated IL-10 responses, leading to regulatory T cells (Treg) phenotype differentiation. Furthermore, the synthetic peptide was able to decrease leukocytes rolling in BALB/C mice and neutrophils migration during inflammatory process in C57BL/6 mice. These data suggest that this peptide may be useful for the treatment of inflammatory diseases, especially because it displays potent anti-inflammatory properties and do not exhibit neutrophils' chemoattraction.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Materiales Biomiméticos/farmacología , Rodamiento de Leucocito/efectos de los fármacos , Neutrófilos/inmunología , Péptidos/farmacología , Factor de Crecimiento Transformador beta1/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Materiales Biomiméticos/química , Femenino , Humanos , Interleucina-10/inmunología , Rodamiento de Leucocito/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Neutrófilos/patología , Péptidos/química , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patología , Factor de Crecimiento Transformador beta1/química , Factor de Necrosis Tumoral alfa/inmunología
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