A Short Peptide That Mimics the Binding Domain of TGF-β1 Presents Potent Anti-Inflammatory Activity

  • PLoS One. 2015 Aug 27;10(8):e0136116. doi: 10.1371/journal.pone.0136116.
Emília R Vaz  1 ,  Patrícia T Fujimura  1 ,  Galber R Araujo  1 ,  Carlos A T da Silva  1 ,  Rangel L Silva  2 ,  Thiago M Cunha  2 ,  Mônica Lopes-Ferreira  3 ,  Carla Lima  3 ,  Márcio J Ferreira  3 ,  Jair P Cunha-Junior  4 ,  Ernesto A Taketomi  4 ,  Luiz R Goulart  5 ,  Carlos Ueira-Vieira  1
Affiliations
  • 1. Laboratory of Nanobiotechnology Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
  • 2. Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • 3. Immunoregulation Unit, Special Laboratory of Applied Toxicology (CEPID/FAPESP), Butantan Institute, São Paulo, São Paulo State, Brazil.
  • 4. Laboratory of Immunotechnology and Immunochemistry, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
  • 5. Laboratory of Nanobiotechnology Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil; Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, United States of America.
PMID: 26312490 DOI: 10.1371/journal.pone.0136116
Abstract

The transforming growth factor beta 1 (TGF-β1) is a pleiotropic cytokine with multiple roles in development, wound healing, and immune regulation. TGF-β1-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-β-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-β1 function with higher potency. Specific mimetic peptides were obtained through a PhD subtraction strategy from whole cell binding using TGF-β1 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-β1 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.

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