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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
- 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.
- Subjects :
- 0301 basic medicine
lcsh:Immunologic diseases. Allergy
Endothelin A Receptor Antagonists
medicine.drug_class
T-Lymphocytes
CD3
T cell
Immunology
Inflammation
Pharmacology
Peptides, Cyclic
Mice
03 medical and health sciences
polymorphonuclear myeloid-derived suppressor cells
0302 clinical medicine
medicine
Animals
Immunology and Allergy
Colitis
T-cell dependent manner
Original Research
STAT6
Mice, Inbred BALB C
biology
business.industry
Myeloid-Derived Suppressor Cells
Pneumonia
Receptor antagonist
medicine.disease
BQ123
acute inflammation
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Acute Disease
Knockout mouse
Myeloid-derived Suppressor Cell
biology.protein
cardiovascular system
endothelin-A receptor antagonist
Chemical and Drug Induced Liver Injury
medicine.symptom
business
lcsh:RC581-607
Granulocytes
Subjects
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