科研之友
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摘要
The transforming growth factor beta 1 (TGF-beta 1) is a pleiotropic cytokine with multiple roles in development, wound healing, and immune regulation. TGF-beta 1-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-beta-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-beta 1 function with higher potency. Specific mimetic peptides were obtained through a PhD subtraction strategy from whole cell binding using TGF-beta 1 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-alpha and IL-10 cytokines. The synthetic pm26TGF-beta 1 peptide tested in PBMC significantly down-modulated TNF-alpha 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.
- 出版日期2015-8-27
