title: A Short Peptide That Mimics the Binding Domain of TGF-β1 Presents Potent Anti-Inflammatory Activity.
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.
authors: Laboratory of Nanobiotechnology Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Emília R
authors: ER
authors: Vaz
authors: Laboratory of Nanobiotechnology Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Patrícia T
authors: PT
authors: Fujimura
authors: Laboratory of Nanobiotechnology Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Galber R
authors: GR
authors: Araujo
authors: Laboratory of Nanobiotechnology Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Carlos A T
authors: CA
authors: da Silva
authors: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors: Rangel L
authors: RL
authors: Silva
authors: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors: Thiago M
authors: TM
authors: Cunha
authors: Immunoregulation Unit, Special Laboratory of Applied Toxicology (CEPID/FAPESP), Butantan Institute, São Paulo, São Paulo State, Brazil.
authors: Mônica
authors: M
authors: Lopes-Ferreira
authors: Immunoregulation Unit, Special Laboratory of Applied Toxicology (CEPID/FAPESP), Butantan Institute, São Paulo, São Paulo State, Brazil.
authors: Carla
authors: C
authors: Lima
authors: Immunoregulation Unit, Special Laboratory of Applied Toxicology (CEPID/FAPESP), Butantan Institute, São Paulo, São Paulo State, Brazil.
authors: Márcio J
authors: MJ
authors: Ferreira
authors: Laboratory of Immunotechnology and Immunochemistry, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Jair P
authors: JP
authors: Cunha-Junior
authors: Laboratory of Immunotechnology and Immunochemistry, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Ernesto A
authors: EA
authors: Taketomi
authors: 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.
authors: Luiz R
authors: LR
authors: Goulart
authors: Laboratory of Nanobiotechnology Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Carlos
authors: C
authors: Ueira-Vieira
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D036904:Leukocyte Rolling / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C508609:IL10 protein, human; D010455:Peptides; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10