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Estrogen-regulated STAT1 activation promotes TLR8 expression to facilitate signaling via microRNA-21 in systemic lupus erythematosus.
Young, Nicholas A; Valiente, Giancarlo R; Hampton, Jeffrey M; Wu, Lai-Chu; Burd, Craig J; Willis, William L; Bruss, Michael; Steigelman, Holly; Gotsatsenko, Maya; Amici, Stephanie A; Severin, Mary; Claverie, Lucila Marino; Guerau-de-Arellano, Mireia; Lovett-Racke, Amy; Ardoin, Stacy; Jarjour, Wael N.
Afiliação
  • Young NA; Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Valiente GR; Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Hampton JM; Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Wu LC; Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Burd CJ; Department of Molecular Genetics, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Willis WL; Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Bruss M; Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Steigelman H; Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Gotsatsenko M; Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Amici SA; School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, and Department of Neuroscience, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Severin M; Department of Microbial Infection and Immunity, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Claverie LM; Department of Rheumatology, Hospital Bernardino Rivadavia, Buenos Aires, Argentina.
  • Guerau-de-Arellano M; School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, and Department of Neuroscience, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Lovett-Racke A; Department of Microbial Infection and Immunity, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Ardoin S; Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
  • Jarjour WN; Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA. Electronic address: Wael.Jarjour@osumc.edu.
Clin Immunol ; 176: 12-22, 2017 03.
Article em En | MEDLINE | ID: mdl-28039018
ABSTRACT
Recent studies implicate innate immunity to systemic lupus erythematosus (SLE) pathogenesis. Toll-like receptor (TLR)8 is estrogen-regulated and binds viral ssRNA to stimulate innate immune responses, but recent work indicates that microRNA (miR)-21 within extracellular vesicles (EVs) can also trigger this receptor. Our objective was to examine TLR8 expression/activation to better understand sex-biased responses involving TLR8 in SLE. Our data identify an estrogen response element that promotes STAT1 expression and demonstrate STAT1-dependent transcriptional activation of TLR8 with estrogen stimulation. In lieu of viral ssRNA activation, we explored EV-encapsulated miR-21 as an endogenous ligand and observed induction of both TLR8 and cytokine expression in vitro. Moreover, extracellular miR detection was found predominantly within EVs. Thus, just as a cytokine or chemokine, EV-encapsulated miR-21 can act as an inflammatory signaling molecule, or miRokine, by virtue of being an endogenous ligand of TLR8. Collectively, our data elucidates a novel innate inflammatory pathway in SLE.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / MicroRNAs / Estrogênios / Fator de Transcrição STAT1 / Receptor 8 Toll-Like / Lúpus Eritematoso Sistêmico Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / MicroRNAs / Estrogênios / Fator de Transcrição STAT1 / Receptor 8 Toll-Like / Lúpus Eritematoso Sistêmico Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article