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Protease-activated receptor 4 plays a role in lipopolysaccharide-induced inflammatory mechanisms in murine macrophages.
Barra, A; Freitas, K M; Marconato, D G; Faria-Pinto, P; Lopes, M T P; Klein, André.
Afiliação
  • Barra A; Laboratory of Pain and Inflammation, Department of Pharmacology, Institute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Av. Presidente Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31270-010, Brazil.
  • Freitas KM; Laboratory of Antitumoral Substances, Department of Pharmacology, ICB, UFMG, Belo Horizonte, MG, Brazil.
  • Marconato DG; Protein Structure and Function Study Laboratory, Department of Biochemistry, ICB, Federal University of Juiz de Fora (UFJF), Juiz de Fora, MG, Brazil.
  • Faria-Pinto P; Protein Structure and Function Study Laboratory, Department of Biochemistry, ICB, Federal University of Juiz de Fora (UFJF), Juiz de Fora, MG, Brazil.
  • Lopes MTP; Laboratory of Antitumoral Substances, Department of Pharmacology, ICB, UFMG, Belo Horizonte, MG, Brazil.
  • Klein A; Laboratory of Pain and Inflammation, Department of Pharmacology, Institute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Av. Presidente Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31270-010, Brazil. klein@ufmg.br.
Naunyn Schmiedebergs Arch Pharmacol ; 394(5): 853-862, 2021 05.
Article em En | MEDLINE | ID: mdl-33159803
The role of protease-activated receptor (PAR)4 in thrombin-induced platelet aggregation has been studied, and PAR4 blockade is thought to be useful as a new and promising approach in antiplatelet therapy in humans. In recent years, studies have been conducted to clarify the role of PAR4 in the host defense against invading microorganisms and pathogen-induced inflammation; however, to date, the role of PAR4 in mediating the LPS-induced inflammatory repertoire in macrophages remains to be elucidated. Here, we investigated the effects of the synthetic PAR4 agonist peptide (PAR4-AP) AYPGKF-NH2 on the phagocytosis of zymosan-FITC particles; NO, ROS, and iNOS expression; and cytokine production in C57/BL6 macrophages cocultured with PAR4-AP/LPS. The PAR4-AP impaired LPS-induced and basal phagocytosis, which was restored by pharmacological PAR4 blockade. Coincubation with the PAR4-AP/LPS enhanced NO and ROS production and iNOS expression; decreased IL-10, but not TNF-α, in the culture supernatant; and increased translocation of the p65 subunit of the proinflammatory gene transcription factor NF-κ-B. Our results provide evidence for a complex mechanism and new approach by which PAR4 mediates the macrophage response triggered by LPS through counter-regulating the phagocytic activity of macrophages and innate response mechanisms implicated in the killing of invading pathogens.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligopeptídeos / Receptores de Trombina / Inflamação / Macrófagos Limite: Animals Idioma: En Revista: Naunyn Schmiedebergs Arch Pharmacol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligopeptídeos / Receptores de Trombina / Inflamação / Macrófagos Limite: Animals Idioma: En Revista: Naunyn Schmiedebergs Arch Pharmacol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha