Angiotensin II Type 1 Receptor Knockdown Impairs Interleukin-1 beta-Induced Cytokines in Human Periodontal Fibroblasts

Autor(es)

Gabriele, Lilian Gobbo ; Morandini, Ana Carolina ; Dionisio, Thiago Jose ; Santos, Carlos Ferreira

• Tipo de documento: Artigo Científico
• Fonte: Journal of Periodontology; v. 88, n. 1, p. E1-E11, JAN 2017.
• Citações Web of Science: 1

Resumo

Background: The renin-angiotensin (Ang) system (RAS) has been reported as an important modulator of inflammatory and immune responses. Evidence suggests an alternative Ang 1-7/Mas receptor axis as counter-regulatory to the classic RAS Ang II/Ang II Type 1 (AT1) receptor axis. It is known that periodontal pathogens elicit host-derived immune response due to release of cytokines such as interleukin (IL)-1 beta, and fibroblasts are among the most numerous sentinel cells that contribute to this production. The aim of this study is to determine whether AT1 receptor (AT1R) contributes to production of inflammatory cytokines that are important for periodontal pathogenesis using primary human gingival fibroblasts (HGFs) and human periodontal ligament fibroblasts (HPLFs) stimulated with IL-1 beta. Methods: Through RNA interference or pharmacologic inhibition using AT1R antagonist losartan, HGF and HPLF were stimulated by IL-1 beta for 3 (messenger RNA {[}mRNA]) or 24 (protein) hours. Results: IL-1 beta upregulated mRNA expression of AT1R, IL-1 beta, IL-6, IL-8, tumor necrosis factor-alpha, and osteoprotegerin (OPG) in HGF and HPLF. AT1R knockdown impaired IL-1 beta-induced IL-6 and IL-8 secretion in cultured HGF and HPLF. AT1R silencing also increased OPG gene expression in HGF only. Pharmacologic inhibition of AT1R through losartan modulated mRNA transcription of IL-6 and IL-8 in HPLF but not in HGF. In contrast, IL-1b-induced secretion of IL-6 and IL-8 was not influenced by losartan in HGF or HPLF. Conclusion: These results suggest that AT1R knockdown and AT1R pharmacologic blockade by losartan may differently control balance of inflammatory cytokines, such as IL-6 and IL-8, in primary human periodontal fibroblasts. (AU)

• Processo FAPESP: 13/16113-9 - Papel da sinalização pelo receptor purinérgico P2X7 e das deacetilases de histona na resposta imune inata de fibroblastos humanos periodontais: implicações na patogênese da periodontite
• Beneficiário: Ana Carolina Morandini Ramos
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/20954-4 - Papel da enzima Nucleosídeo Difosfato Quinase de Porphyromonas Gingivalis na modulação epigenética do receptor purinérgico P2X7
• Beneficiário: Ana Carolina Morandini Ramos
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 15/03965-2 - Papel do sistema renina-angiotensina em diferentes modelos inflamatórios orais: uma abordagem interdisciplinar experimental e clínica
• Beneficiário: Carlos Ferreira dos Santos
• Linha de fomento: Auxílio à Pesquisa - Temático