Activation of Toll-Like Receptor 3 Induces Interleukin-1 Receptor Antagonist Expression by Activating the Interferon Regulatory Factor 3.
J Innate Immun
; 12(4): 304-320, 2020.
Article
in En
| MEDLINE
| ID: mdl-31865314
ABSTRACT
Toll-like receptor 3 (TLR3) is a sensor of endogenous cell necrosis during the process of acute inflammation. Interleukin (IL)-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine and can negatively regulate the pathogenesis of inflammation. However, whether and how activation of TLR3 can regulate IL-1Ra expression has not been clarified. Here, we show that poly(IC) induces IL-1Ra expression in primarily cultured human fibroblast-like synoviocytes and other types of cells. Induction of IL-1Ra by poly(IC) was dependent on TLR3, but was independent of melanoma differentiation--associated protein 5 or retinoic acid-inducible gene I. Interferon regulatory factor 3 (IRF3) directly binds to the IL-1Ra promoter and promotes IL-1Ra expression in response to poly(IC) stimulation. Induction of IL-1Ra by poly(IC) was abolished by the inhibition of the NF-κB signaling, attenuated by the inhibition of the PI3K-Akt signaling, enhanced by inhibition of the ERK1/2 or MSK1/2 activation, but was independent of the p38 MAPK signaling. Treatment with poly(IC) or Sendai virus elevated the levels of serum IL-1Ra in wild-type, but not in TLR3-/- or IRF3-/- mice. Our findings may provide new insights into the intrinsic anti-inflammatory function of TLR3 and double-stranded RNA-induced IL-Ra expression by TLR3 and its regulation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Toll-Like Receptor 3
/
Interleukin 1 Receptor Antagonist Protein
Limits:
Animals
/
Humans
Language:
En
Journal:
J Innate Immun
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2020
Document type:
Article
Affiliation country:
China