DAP1-2: a synthetic peptide targeting IL-1R1 receptor effectively suppresses IL-1β in vitro.

Autor: De-Pieri E; Laboratório de Fisiopatologia Experimental, Programa de Pós Graduação Em Ciências da Saúde, Universidade Do Extremo Sul CatarinenseCriciúma, Santa Catarina, Brazil., Zaccaron RP; Laboratório de Fisiopatologia Experimental, Programa de Pós Graduação Em Ciências da Saúde, Universidade Do Extremo Sul CatarinenseCriciúma, Santa Catarina, Brazil., Mezzari CG; Laboratório de Fisiopatologia Experimental, Programa de Pós Graduação Em Ciências da Saúde, Universidade Do Extremo Sul CatarinenseCriciúma, Santa Catarina, Brazil., Cardoso MM; Programa de Pós-Graduação Em Ciências da Saúde: Infectologia E Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., De Roch Casagrande L; Laboratório de Fisiopatologia Experimental, Programa de Pós Graduação Em Ciências da Saúde, Universidade Do Extremo Sul CatarinenseCriciúma, Santa Catarina, Brazil., Silveira PCL; Laboratório de Fisiopatologia Experimental, Programa de Pós Graduação Em Ciências da Saúde, Universidade Do Extremo Sul CatarinenseCriciúma, Santa Catarina, Brazil. psilveira@unesc.net., Machado-de-Ávila RA; Laboratório de Fisiopatologia Experimental, Programa de Pós Graduação Em Ciências da Saúde, Universidade Do Extremo Sul CatarinenseCriciúma, Santa Catarina, Brazil.
Jazyk: angličtina
Zdroj: Immunologic research [Immunol Res] 2024 Aug; Vol. 72 (4), pp. 788-796. Date of Electronic Publication: 2024 May 02.
DOI: 10.1007/s12026-024-09485-6
Abstrakt: The pathological manifestation of the inflammatory process primarily stems from the heightened release of pro-inflammatory cytokines, with IL-1β standing out as a pivotal cytokine. The excessive presence of IL-1β disrupts immune signaling, thereby assuming a pathogenic and exacerbating role in the pathophysiology of numerous inflammatory diseases. Regulating IL-1β levels becomes crucial, and the IL-1Ra molecule serves this purpose by binding to the IL-1R1 receptor, thereby impeding the binding of IL-1β. Several pharmaceuticals have entered the market, aiming to neutralize IL-1β's biological function through diverse mechanisms. However, the existing IL-1β inhibitors are recombinant proteins, characterized by a high production cost and limited stability. Therefore, this study aimed to predict a peptide, named DAP1-2, based on the IL-1Ra molecule. DAP1-2 was designed to attenuate responses triggered by IL-1β by blocking the IL-1R1 receptor. The selection of amino acids from the IL-1Ra molecule (PDB: I1RA) that interact with the three domains of the IL-1R1 receptor was performed using Swiss PDB Viewer. After prediction, chemical synthesis was made using the Fmoc-Synthesis technique. The efficacy of DAP1-2 was assessed using RAW 264.7 cells, which were exposed to LPS (5 μg/mL) for 24 h to induce IL-1β expression and treated with the peptides in different concentrations. IL-1β levels were assessed using ELISA, and the gene expression of IL-1β was measured by RT-qPCR, additionally to the viability test. Results revealed a significant reduction in IL-1β levels and gene expression in cells stimulated by LPS and treated with DAP1-2 in different concentrations. Furthermore, the MTT assay confirmed the nontoxic nature of the peptides on the cell lineage. This alternative approach shows promise as an IL-1 inhibitor, due to the stability, ease of production, and cost-effectiveness provided by the use of synthetic peptides.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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