| RRC ID |
58372
|
| Author |
Liu Y, Mo CF, Luo XY, Li H, Guo HJ, Sun H, Hu S, Li LM, Wang YT, Yang SX, Chang S, Zou Q.
|
| Title |
Activation of Toll-Like Receptor 3 Induces Interleukin-1 Receptor Antagonist Expression by Activating the Interferon Regulatory Factor 3.
|
| Journal |
J Innate Immun
|
| 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(I:C) induces IL-1Ra expression in primarily cultured human fibroblast-like synoviocytes and other types of cells. Induction of IL-1Ra by poly(I:C) 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(I:C) stimulation. Induction of IL-1Ra by poly(I:C) 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(I:C) 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.
|
| Volume |
12(4)
|
| Pages |
304-320
|
| Published |
2020-1-1
|
| DOI |
10.1159/000504321
|
| PII |
000504321
|
| PMID |
31865314
|
| PMC |
PMC7383292
|
| MeSH |
Animals
Cell Line
Humans
Inflammation / chemically induced
Inflammation / genetics
Inflammation / immunology
Interferon Regulatory Factor-3 / genetics
Interleukin 1 Receptor Antagonist Protein / genetics
Interleukin 1 Receptor Antagonist Protein / immunology*
Mice
Mice, Knockout
Poly I-C / pharmacology
Toll-Like Receptor 3 / genetics
Toll-Like Receptor 3 / immunology*
|
| IF |
4.932
|
| Times Cited |
1
|
| Resource |
| Mice |
RBRC00858 |
