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

Chen, Ziyang; Zhang, Xiaogang; Lv, Shuaijun; Xing, Zhe; Shi, Mengyu; Li, Xinyao; Chen, Meiqi; Zuo, Shaowen; Tao, Yingxu; Xiao, Gang; Liu, Jingping; He, Yumei

doi:10.3389/fimmu.2021.641874

Cited by 7 publications

(10 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ILC2s have been recently recognized for their central role in both initiating and perpetuating asthma-related lung inflammation (14)(15)(16)(17)(18)(19)(20). In addition, our group recently reported that the ETAR antagonist BQ123 attenuates papain-induced pneumonia (42). Therefore, in this study, we explored the relationship between ILC2s and BQ123 in pneumonia.…”

Section: Bq13 Exhibited Protective Effects Against Alternaria Alterna...mentioning

confidence: 96%

“…Lung function was assessed by lung resistance and dynamic compliance in anesthetized tracheostomized mice, via the Electro-Medical Measurement Systems (EMMS) and EMMS Data Acquisition software (Electromedsys supporting sciences Co Ltd, UK), and mice were synchronously challenged with aerosolized increasing doses of methacholine (0, 5, 10, 25, 50 mg/ ml). Then, the experimental protocol for tissue preparation was described previously by Chen et al (42). Briefly, the trachea was cannulated and the lungs were lavaged twice with 1 mL ice-cold PBS to collect BALF cells.…”

Section: Measurement Of Lung Function and Isolation Of Mononuclear Ce...mentioning

confidence: 99%

“…Another ETAR antagonist BQ123 is used to treat cardiovascular diseases, such as hypertension, diabetic retinopathy, and ischemia/reperfusion injury (37)(38)(39)(40). Moreover, BQ123 relieves chronic airway inflammatory obstructive asthma (COA) (41) and acute inflammatory diseases (42). Therefore, BQ123 may be a promising therapeutic target in asthma; however, this needs to be investigated further in future studies.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

et al. 2022

Self Cite

View full text Add to dashboard Cite

Allergic airway inflammation is a universal airway disease that is driven by hyperresponsiveness to inhaled allergens. Group 2 innate lymphoid cells (ILC2s) produce copious amounts of type 2 cytokines, which lead to allergic airway inflammation. Here, we discovered that both peripheral blood of human and mouse lung ILC2s express the endothelin-A receptor (ETAR), and the expression level of ETAR was dramatically induced upon interleukin-33 (IL-33) treatment. Subsequently, both preventive and therapeutic effects of BQ123, an ETAR antagonist, on allergic airway inflammation were observed, which were associated with decreased proliferation and type 2 cytokine productions by ILC2s. Furthermore, ILC2s from BQ123 treatment were found to be functionally impaired in response to an interleukin IL-33 challenged. And BQ123 treatment also affected the phosphorylation level of the extracellular signal-regulated kinase (ERK), as well as the level of GATA binding protein 3 (GATA3) in activated ILC2s. Interestingly, after BQ123 treatment, both mouse and human ILC2s in vitro exhibited decreased function and downregulation of ERK signaling and GATA3 stability. These observations imply that ETAR is an important regulator of ILC2 function and may be involved in ILC2-driven pulmonary inflammation. Therefore, blocking ETAR may be a promising therapeutic strategy for allergic airway inflammation.

show abstract

Section: Bq13 Exhibited Protective Effects Against Alternaria Alterna...mentioning

confidence: 96%

Section: Measurement Of Lung Function and Isolation Of Mononuclear Ce...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Human LOX1 + cells were sorted using an EasySep™ Human APC Positive Selection Kit II (Stemcell, Canada). Mouse CD3 + T cells and Gr1 + (mostly Ly6G + ) cells were isolated to a purity of ≥90%, as previously reported 27 …”

Section: Methodsmentioning

confidence: 99%

Polymorphonuclear myeloid-derived suppressor cells link inflammation and damage response after trauma

Liu

Xing

et al. 2021

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

Elimination of the posttraumatic inflammatory response and recovery of homeostasis are crucial for the positive prognosis of trauma patients. Myeloid‐derived suppressor cells (MDSCs) are known to play a regulatory role in the posttraumatic immune response in mice, but their induction source and involved potential mechanism are poorly understood. Here, we report that polymorphonuclear MDSCs (PMN‐MDSCs) are activated after trauma and are closely associated with the progression of the posttraumatic inflammatory response. In humans, lectin‐type oxidized LDL receptor 1 (LOX1) was used to specifically characterize LOX1+ PMN‐MDSCs. Trauma patients showed high intracellular reactive oxygen species (ROS) production, as well as activation of LOX1+ PMN‐MDSCs. These MDSCs contribute to the anti‐inflammatory immune response by regulating the Treg/Th17 and Th2/Th1 balances after trauma, increasing the levels of anti‐inflammatory factors, and decreasing the levels of proinflammatory factors. The number of LOX1+ PMN‐MDSCs was positively correlated with the positive clinical prognosis of trauma patients with infection. Activation of LOX1+ PMN‐MDSCs is mediated by NF‐κB signal, and TGF‐β1 may be as an important inducer for LOX1+ PMN‐MDSCs in the posttraumatic cytokine environment. In a pseudofracture trauma mouse model, we also observed the activation of PMN‐MDSCs, accompanying high levels of intracellular ROS production, NF‐κB phosphorylation, and changes in the inflammatory environment, in particularly by regulating the Treg/Th17 and Th2/Th1 balance. And more significantly, posttraumatic inflammation was alleviated in mice after transferring trauma‐derived PMN‐MDSCs, but aggravated after injecting with Gr1 agonistic antibody. These findings provide evidence for the specific role of PMN‐MDSCs in the regulation of posttraumatic inflammation.

show abstract

“…ET signaling mediates strong vasoconstrictor properties, and the ET A receptor antagonist, BQ123, is an effective therapy for hypertension and obese cardiomyopathy ( 61 ). Recently, BQ123 was shown to induce PMN-MDSC-mediated immune suppression in dextran sulfate sodium-induced colitis, papain-induced pneumonia, and concanavalin A-induced hepatitis in mice ( 62 ). Both the treatment of BQ123, as well as the transfer of BQ123-induced PMN-MDSCs were effective in dampening inflammation ( 62 ).…”

Section: Pharmacological Approaches To Modulate Mdscsmentioning

confidence: 99%

Pharmacological modulation of myeloid-derived suppressor cells to dampen inflammation

2022

View full text Add to dashboard Cite

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population with potent suppressive and regulative properties. MDSCs’ strong immunosuppressive potential creates new possibilities to treat chronic inflammation and autoimmune diseases or induce tolerance towards transplantation. Here, we summarize and critically discuss different pharmacological approaches which modulate the generation, activation, and recruitment of MDSCs in vitro and in vivo, and their potential role in future immunosuppressive therapy.

show abstract

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

Cited by 7 publications

References 62 publications

Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

Polymorphonuclear myeloid-derived suppressor cells link inflammation and damage response after trauma

Pharmacological modulation of myeloid-derived suppressor cells to dampen inflammation

Contact Info

Product

Resources

About