title: Angiotensin II Type 1 Receptor Knockdown Impairs Interleukin-1β-Induced Cytokines in Human Periodontal Fibroblasts.
abstract: 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)-1β, 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-1β.
  
  
  
  Through RNA interference or pharmacologic inhibition using AT1R antagonist losartan, HGF and HPLF were stimulated by IL-1β for 3 (messenger RNA [mRNA]) or 24 (protein) hours.
  
  
  
  IL-1β upregulated mRNA expression of AT1R, IL-1β, IL-6, IL-8, tumor necrosis factor-alpha, and osteoprotegerin (OPG) in HGF and HPLF. AT1R knockdown impaired IL-1β-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-1β-induced secretion of IL-6 and IL-8 was not influenced by losartan in HGF or HPLF.
  
  
  
  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.
authors.affiliation: Department of Biological Sciences, Discipline of Pharmacology, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil.
authors.forename: Lilian Gobbo
authors.initials: LG
authors.lastname: Gabriele
authors.affiliation: Department of Biological Sciences, Discipline of Pharmacology, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil.|Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Morandini
authors.affiliation: Department of Biological Sciences, Discipline of Pharmacology, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil.
authors.forename: Thiago José
authors.initials: TJ
authors.lastname: Dionísio
authors.affiliation: Department of Biological Sciences, Discipline of Pharmacology, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil.
authors.forename: Carlos Ferreira
authors.initials: CF
authors.lastname: Santos
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology*; D010513:Periodontal Ligament / Q000166:cytology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan
keywords: Angiotensins; angiotensin receptor antagonists; cytokines; fibroblasts; periodontium; renin-angiotensin system