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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Gabriele, Lilian Gobbo ; Morandini, Ana Carolina ; Dionisio, Thiago Jose ; Santos, Carlos Ferreira
Total Authors: 4
Document type: Journal article
Source: Journal of Periodontology; v. 88, n. 1, p. E1-E11, JAN 2017.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 13/16113-9 - Signaling by purinergic receptor P2X7 and histone deacetylases in the innate immune response of human periodontal fibroblasts: implications in the pathogenesis of periodontitis
Grantee:Ana Carolina Morandini Ramos
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 15/03965-2 - Role of the renin-angiotensin system in different oral inflammatory models: an experimental interdisciplinary and clinical approach
Grantee:Carlos Ferreira dos Santos
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 15/20954-4 - The role of Porphyromonas gingivalis-Nucleoside diphosphate kinase in epigenetic modulation of P2X7 receptor
Grantee:Ana Carolina Morandini Ramos
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor