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Estrogen-regulated STAT1 activation promotes TLR8 expression to facilitate signaling via microRNA-21 in systemic lupus erythematosus.
- Source :
-
Clinical immunology (Orlando, Fla.) [Clin Immunol] 2017 Mar; Vol. 176, pp. 12-22. Date of Electronic Publication: 2016 Dec 27. - Publication Year :
- 2017
-
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.<br /> (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Line, Tumor
Chemokines metabolism
Humans
Immunity, Innate immunology
Inflammation immunology
Inflammation metabolism
Ligands
Lupus Erythematosus, Systemic immunology
MCF-7 Cells
Estrogens metabolism
Lupus Erythematosus, Systemic metabolism
MicroRNAs metabolism
STAT1 Transcription Factor metabolism
Signal Transduction physiology
Toll-Like Receptor 8 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1521-7035
- Volume :
- 176
- Database :
- MEDLINE
- Journal :
- Clinical immunology (Orlando, Fla.)
- Publication Type :
- Academic Journal
- Accession number :
- 28039018
- Full Text :
- https://doi.org/10.1016/j.clim.2016.12.005