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Treatment With Endothelin-A Receptor Antagonist BQ123 Attenuates Acute Inflammation in Mice Through T-Cell-Dependent Polymorphonuclear Myeloid-Derived Suppressor Cell Activation

Authors :
Ziyang Chen
Xiaogang Zhang
Shuaijun Lv
Zhe Xing
Mengyu Shi
Xinyao Li
Meiqi Chen
Shaowen Zuo
Yingxu Tao
Gang Xiao
Jingping Liu
Yumei He
Source :
Frontiers in Immunology, Vol 12 (2021), Frontiers in Immunology
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

The endothelin-A receptor antagonist BQ123 is an effective treatment agent for hypertension and obese cardiomyopathy. However, the role of BQ123 in controlling acute inflammatory diseases and its underlying mechanisms are not well understood. Here, we showed that BQ123 activated polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in mice and that the IL13/STAT6/Arg1 signaling pathway is involved in this process. Importantly, both treatment with BQ123 and the transfer of BQ123-induced PMN-MDSCs (BQ123-MDSCs) were effective in relieving inflammation, including dextran sulfate sodium (DSS)-induced colitis, papain-induced pneumonia, and concanavalin A (ConA)-induced hepatitis, in mice. The treatment effects were mediated by the attenuation of the inflammation associated with the accumulation of PMN-MDSCs in the colon, lung, and liver. However, concurrent injection of Gr1 agonistic antibody with BQ123 induced PMN-MDSC aggravated the observed acute inflammation. Interestingly, no remission of inflammation was observed in Rag2 knockout mice administered BQ123-MDSCs, but co-injection with CD3+ T cells significantly relieved acute inflammation. In summary, BQ123-induced PMN-MDSCs attenuated acute inflammation in a T cell-dependent manner, providing a novel potential strategy to prevent the occurrence of acute inflammation.

Details

Language :
English
ISSN :
16643224
Volume :
12
Database :
OpenAIRE
Journal :
Frontiers in Immunology
Accession number :
edsair.doi.dedup.....5a1b442a0069cced8f8dab6d2085abf4
Full Text :
https://doi.org/10.3389/fimmu.2021.641874/full