Back to Search
Start Over
Ubiquitin-activating enzyme E1 inhibitor PYR41 attenuates angiotensin II-induced activation of dendritic cells via the I κ Ba/ NF- κ B and MKP1/ ERK/ STAT1 pathways.
- Source :
- Immunology; Jun2014, Vol. 142 Issue 2, p307-319, 13p
- Publication Year :
- 2014
-
Abstract
- The activation of dendritic cells ( DCs) is necessary to initiate immune responses. Angiotensin II ( Ang II) can enhance the maturation and activation of DCs, but the mechanisms are still unclear. Ubiquitin-activating enzyme ( E1/ Uba1) is the common first step in ubiquitylation, which decides whether or not the modified protein is ultimately degraded by the proteasome. This study aimed to investigate the role of E1 in Ang II-induced activation of DCs and the underlying mechanisms. First, we showed that Ang II stimulation significantly up-regulated E1 expression in DCs. Moreover, Ang II treatment markedly induced phenotypic maturation, the secretion of cytokines and the immunostimulatory capacity of DCs. In contrast, inhibition of E1 by a small molecule inhibitor, 4 [4-(5-nitro-furan-2-ylmethylene)-3, 5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester ( PYR41), markedly attenuated these effects. Mechanistically, PYR41 treatment markedly decreased K63-linked ubiquitination of tumour necrosis factor receptor-associated factor 6 and nuclear factor- κ B essential modulator, inhibited proteasomal degradation of nuclear factor- κ B inhibitor α and mitogen-activated protein kinase phosphatase 1 thereby resulting in activation of nuclear factor- κ B, extracellular signal-regulated kinase 1/2 and signal transducer and activator of transcription 1 signalling pathways in DCs induced by Ang II. Taken together, our results demonstrate a novel role of E1 in Ang II-induced activation of DCs, and inhibition of E1 activity might be a potential therapeutic target for DC-mediated autoimmune diseases. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00192805
- Volume :
- 142
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 95701971
- Full Text :
- https://doi.org/10.1111/imm.12255