Mapeamento de peptídeos ligantes ao receptor do fator de necrose tumoral alfa

Abstract

Tumor necrosis factor α (TNF-α) is an important proinflammatory in immune responses against antigens. Its activation triggers inflammation and signaling to other immune components to promote inflammatory processes. However, failure in the TNF-α regulation may determine the pathological development, such cancer and rheumatoid arthritis. The objective of this study was to map and characterize peptides binding to TNF- α receptor (TNFR) by Phage Display in order to select some immunomodulatory peptides. The selection of these peptides was performed using peripheral blood mononuclear cells (PBMC) from healthy donor as source TNFR. After selection and pre-screening three peptides were synthesized. After in vitro PBMC stimulation two of them (PhDTNF-7 and PhDTNF-9) were able to significantly increase interleukin 1β (IL-1β, p < 0.05), a pro- inflammatory cytokine. Also in vitro, those peptides are efficient to increase the serine 536 phosphorylation of the nuclear factor kappa B (NF-kB), a biomarker for TNF-α pathway activation. Synthetic implants in mice were injected with peptide and same biochemical biomarker to test the effect in immune neutrophil biomarker) and N-acetyl- D-β-glucosaminidase (NAG, macrophage biomarker). Among the three selected peptides, only the PhDTNF-9 could be validated as TNF-α mimetic.