Diminazene aceturate inhibits the SARS-CoV-2 spike protein-induced inflammation involving leukocyte migration and DNA extracellular traps formation.

Autor: Pereira-Silva GC; Laboratory on Innate Immunity, Department of Immunology, Institute of Microbiology Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil., Cornélio CKCA; Biotechnology and Biodiversity Center Research, Laboratory of Inflammation and Translational Gastroenterology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba, PI, Brazil., Pacheco G; Department of Biochemistry and Pharmacology, Health Sciences Center, Universidade Federal do Piauí (UFPI), Teresina, PI, Brazil., Rochael NC; Laboratory on Innate Immunity, Department of Immunology, Institute of Microbiology Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil., Gomes IAB; Biotechnology and Biodiversity Center Research, Laboratory of Inflammation and Translational Gastroenterology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba, PI, Brazil., Cajado AG; Department of Physiology and Pharmacology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil., Silva KC; Biotechnology and Biodiversity Center Research, Laboratory of Inflammation and Translational Gastroenterology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba, PI, Brazil., Gonçalves BS; Laboratory on Thymus Research, Oswaldo Cruz Institute (Fiocruz), Rio de Janeiro, RJ, Brazil., Temerozo JR; Laboratory on Thymus Research, Oswaldo Cruz Institute (Fiocruz), Rio de Janeiro, RJ, Brazil; National Institute of Science and Technology on Neuroimmunemodulation, Rio de Janeiro, Brazil., Bastos RS; Biotechnology and Biodiversity Center Research, Laboratory of Inflammation and Translational Gastroenterology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba, PI, Brazil., Rocha JA; Biotechnology and Biodiversity Center Research, Laboratory of Inflammation and Translational Gastroenterology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba, PI, Brazil., Souza LP; Biotechnology and Biodiversity Center Research, Laboratory of Inflammation and Translational Gastroenterology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba, PI, Brazil., Souza MHLP; Department of Physiology and Pharmacology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil., Lima-Júnior RCP; Department of Physiology and Pharmacology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil., Medeiros JVR; Biotechnology and Biodiversity Center Research, Laboratory of Inflammation and Translational Gastroenterology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba, PI, Brazil; Department of Biochemistry and Pharmacology, Health Sciences Center, Universidade Federal do Piauí (UFPI), Teresina, PI, Brazil., Filgueiras MC; Biotechnology and Biodiversity Center Research, Laboratory of Inflammation and Translational Gastroenterology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba, PI, Brazil., Bou-Habib DC; Laboratory on Thymus Research, Oswaldo Cruz Institute (Fiocruz), Rio de Janeiro, RJ, Brazil; National Institute of Science and Technology on Neuroimmunemodulation, Rio de Janeiro, Brazil., Saraiva EM; Laboratory on Innate Immunity, Department of Immunology, Institute of Microbiology Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil. Electronic address: esaraiva@micro.ufrj.br., Nicolau LAD; Biotechnology and Biodiversity Center Research, Laboratory of Inflammation and Translational Gastroenterology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba, PI, Brazil; Department of Biochemistry and Pharmacology, Health Sciences Center, Universidade Federal do Piauí (UFPI), Teresina, PI, Brazil. Electronic address: lucasnicolau@ufpi.edu.br.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Sep 01; Vol. 352, pp. 122895. Date of Electronic Publication: 2024 Jul 08.
DOI: 10.1016/j.lfs.2024.122895
Abstrakt: Aims: To investigate the SARS-CoV-2 Spike protein (Spk)-induced inflammatory response and its downmodulation by diminazene aceturate (DIZE).
Materials and Methods: Through inducing Spk inflammation in murine models, leukocyte migration to the peritoneum, levels of myeloperoxidase (MPO), malondialdehyde (MDA), rolling and adhesion of mesenteric leukocytes, and vascular permeability were investigated. Extracellular DNA traps (DETs) induced by Spk and the production of IL-6 and TNF-α were analyzed using human neutrophils, monocytes, and macrophages. In silico assays assessed the molecular interaction between DIZE and molecules related to leukocyte migration and DETs induction.
Key Findings: Spk triggered acute inflammation, demonstrated by increasing leukocyte migration. Oxidative stress was evidenced by elevated levels of MPO and MDA in the peritoneal liquid. DIZE attenuated cell migration, rolling, and leukocyte adhesion, improved vascular barrier function, mitigated DETs, and reduced the production of Spk-induced pro-inflammatory cytokines. Computational studies supported our findings, showing the molecular interaction of DIZE with targets such as β2 integrin, PI3K, and PAD2 due to its intermolecular coupling.
Significance: Our results outline a novel role of DIZE as a potential therapeutic agent for mitigating Spk-induced inflammation.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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