Mas Receptor Activation Attenuates Allergic Airway Inflammation via Inhibiting JNK/CCL2-induced Macrophage Recruitment

Hong, Luna; Chen, Ming; Shi, Jianting; Wang, Qiujie; Guo, Yanxia; Liu, Shanying; Pan, Ruijian; Yuan, Xiaoqing; Jiang, Shanping

doi:10.21203/rs.3.rs-108556/v1

Cited by 3 publications

(7 citation statements)

References 60 publications

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“…Overall, the mechanisms by which Mas receptor blockade intensifies inflammation need to be investigated in more detail. However, these data, together with others studies, consolidated the concept that Ang‐(1‐7)/Mas receptor is an important immunomodulatory pathway (Barroso et al, 2017; Bastos et al, 2020; da Silveira et al, 2010; El‐Hashim et al, 2012, 2019; Hong et al, 2021; Magalhaes et al, 2018; Magalhães et al, 2015; Magalhães et al, 2020, 2021; Rodrigues‐Machado et al, 2013; Tan et al, 2018).…”

Section: An Overview: Renin‐angiotensin System In Asthmamentioning

confidence: 64%

“…Asthmatic patients (Jackson et al, 2020) and mice with allergic pulmonary inflammation have reduced expression of ACE2 (Dhawale et al, 2016). In addition, Mas receptor expression in bronchial epithelium and smooth muscle and pulmonary levels of Ang-(1-7) are reduced in mice with asthma (Hong et al, 2021;Magalhães et al, 2015;Rodrigues-Machado et al, 2013). (El-Hashim et al, 2012;Hong et al, 2021;Magalhães et al, 2015).…”

Section: Angiotensin-(1-7)/mas Pathway In Asthmamentioning

confidence: 99%

“…In addition, Mas receptor expression in bronchial epithelium and smooth muscle and pulmonary levels of Ang-(1-7) are reduced in mice with asthma (Hong et al, 2021;Magalhães et al, 2015;Rodrigues-Machado et al, 2013). (El-Hashim et al, 2012;Hong et al, 2021;Magalhães et al, 2015).…”

Section: Angiotensin-(1-7)/mas Pathway In Asthmamentioning

confidence: 99%

“…El-Hashim et al (2019) showed that the treatment with Ang-(1-7) in asthmatic mice inhibits phosphorylation of Src/EGRF/ERK 1/2 in airway structural cells (El-Hashim et al, 2019). Another study showed that human bronchial epithelial cells stimulated with lipopolysaccharide (LPS) and with AVE 0991 reduces the expression of CCL2 and phosphorylation of JNK, and induces an anti-chemotactic role for macrophages (Hong et al, 2021). Functionally, Ang-(1-7) inhibits the ROCK2 pathway in F I G U R E 2 Representative images of an airway in asthma with inflammation and tissue remodelling and an airway treated under the influence of peptides from the renin-angiotensin system.…”

Section: Angiotensin-(1-7)/mas Pathway In Asthmamentioning

confidence: 99%

“…Treatment with AVE 0991 reduced lung levels of IL‐5 and favoured an increase in the ratio between IL‐10/IL‐5 in mice with allergic pulmonary inflammation (Rodrigues‐Machado et al, 2013). Furthermore, activation of Mas receptors by AVE 0991 in mice with asthma reversed the imbalance between IL‐4 and IL‐10 (Hong et al, 2021). Activation of Mas receptors in asthmatic mice reduces levels of IgE, phosphorylation of mitogen‐activated protein kinase p38 (p38‐MAPK), c‐Jun N‐terminal kinase (JNK) and ERK 1/2, and levels of cytokines IL‐4, IL‐5, GM‐CSF, CCL2, and CCL5 (El‐Hashim et al, 2012; Hong et al, 2021; Magalhães et al, 2015).…”

Section: An Overview: Renin‐angiotensin System In Asthmamentioning

confidence: 99%

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Asthma: role of the angiotensin‐(1‐7)/Mas (MAS1) pathway in pathophysiology and therapy

Gregório

Rodrigues‐Machado²,

Santos

et al. 2021

British J Pharmacology

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The incidence of asthma is a global health problem and requires studies aimed for the development of new treatments to improve its clinical management, reducing personal and economic burdens on the health system. Therefore, the discovery of mediators that promote anti-inflammatory and pro-resolutive effects are highly desirable to improve lung function and quality of life of asthmatic patients. In that regard, experimental studies have shown that the angiotensin-(1-7)/Mas receptor (MAS1) of the renin-angiotensin system is a potential candidate for the treatment of asthma. Therefore, we have reviewed findings related to the function of the angiotensin-(1-7)/Mas pathway in regulating the processes associated with inflammation, including leukocyte influx, fibrogenesis, pulmonary dysfunction and the resolution of inflammation in asthma. Thus, a knowledge of the role of the angiotensin-(1-7)/Mas can help pave the way for the development of new treatments for this disease, which has high morbidity and mortality, through new types of experiments and clinical trials.

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Section: An Overview: Renin‐angiotensin System In Asthmamentioning

confidence: 64%

Section: Angiotensin-(1-7)/mas Pathway In Asthmamentioning

confidence: 99%

Section: Angiotensin-(1-7)/mas Pathway In Asthmamentioning

confidence: 99%

Section: Angiotensin-(1-7)/mas Pathway In Asthmamentioning

confidence: 99%

Section: An Overview: Renin‐angiotensin System In Asthmamentioning

confidence: 99%

See 3 more Smart Citations

Asthma: role of the angiotensin‐(1‐7)/Mas (MAS1) pathway in pathophysiology and therapy

Gregório

Rodrigues‐Machado²,

Santos

et al. 2021

British J Pharmacology

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Activation of the Mas receptors by AVE0991 and MrgD receptor using alamandine to limit the deleterious effects of Ang II‐induced hypertension

Tanriverdi

Özhan

Ulu

et al. 2022

Fundamemntal Clinical Pharma

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The MrgD receptor agonist, alamandine (ALA) and Mas receptor agonist, AVE0991 have recently been identified as protective components of the renin‐angiotensin system. We evaluated the effects of ALA and AVE0991 on cardiovascular function and remodeling in angiotensin (Ang) II‐induced hypertension in rats. Sprague Dawley rats were subject to 4‐week subcutaneous infusions of Ang II (80 ng/kg/min) or saline after which they were treated with ALA (50 μg/kg), AVE0991 (576 μg/kg), or ALA+AVE0991 during the last 2 weeks. Systolic blood pressure (SBP) and heart rate (HR) values were recorded with tail‐cuff plethysmography at 1, 15, and 29 days post‐treatment. After euthanization, the heart and thoracic aorta were removed for further analysis and vascular responses. SBP significantly increased in the Ang II group when compared to the control group. Furthermore, Ang II also caused an increase in cardiac and aortic cyclophilin‐A (CYP‐A), monocyte chemoattractant protein‐1 (MCP‐1), and cardiomyocyte degeneration but produced a decrease in vascular relaxation. HR, matrix metalloproteinase‐2 and ‐9, NADPH oxidase‐4, and lysyl oxidase levels were comparable among groups. ALA, AVE0991, and the drug combination produced antihypertensive effects and alleviated vascular responses. The inflammatory and oxidative stress related to cardiac MCP‐1 and CYP‐A levels decreased in the Ang II+ALA+AVE0991 group. Vascular but not cardiac angiotensin‐converting enzyme‐2 levels decreased with Ang II administration but were similar to the Ang II+ALA+AVE0991 group. Our experimental data showed the combination of ALA and AVE0991 was found beneficial in Ang II‐induced hypertension in rats by reducing SBP, oxidative stress, inflammation, and improving vascular responses.

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Angiotensin-(1-7)/MasR axis promotes migration of monocytes/macrophages with a regulatory phenotype to perform phagocytosis and efferocytosis

Zaidan¹,

Tavares²,

Sugimoto³

et al. 2022

JCI Insight

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Nonphlogistic migration of macrophages contributes to the clearance of pathogens and apoptotic cells: critical steps for the resolution of inflammation and return to homeostasis. Angiotensin-(1-7) [Ang-(1-7)] is an heptapeptide of the Renin-Angiotensin system that acts through Mas receptor (MasR). Ang-(1-7) has recently emerged as a novel pro-resolving mediator, yet Ang-(1-7) resolution mechanisms are not fully determined. Herein, Ang-(1-7) stimulated migration of human and murine monocytes/macrophages in a MasR, CCR2 and MEK/ERK1/2-dependent manner. Pleural injection of Ang-(1-7) promoted nonphlogistic mononuclear cell influx alongside increased levels of CCL2, IL-10 and macrophage polarization towards a regulatory phenotype. Ang-(1-7) induction of CCL2 and mononuclear cell migration was also dependent on MasR and MEK/ERK. Noteworthy, MasR was upregulated during resolution phase of inflammation and their pharmacological inhibition or genetic deficiency impaired mononuclear cell recruitment during self-resolving models of LPS pleurisy and E. coli peritonitis. Inhibition/absence of MasR was associated with reduced CCL2 levels, impaired phagocytosis of bacteria, efferocytosis and delayed resolution of inflammation. In summary, we have uncovered a novel pro-resolving feature of Ang-(1-7), namely the recruitment of mononuclear cells favoring efferocytosis, phagocytosis and resolution of inflammation. Mechanistically, cell migration was dependent on MasR, CCR2 and the MEK/ERK pathway.

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Mas Receptor Activation Attenuates Allergic Airway Inflammation via Inhibiting JNK/CCL2-induced Macrophage Recruitment

Cited by 3 publications

References 60 publications

Asthma: role of the angiotensin‐(1‐7)/Mas (MAS1) pathway in pathophysiology and therapy

Asthma: role of the angiotensin‐(1‐7)/Mas (MAS1) pathway in pathophysiology and therapy

Activation of the Mas receptors by AVE0991 and MrgD receptor using alamandine to limit the deleterious effects of Ang II‐induced hypertension

Angiotensin-(1-7)/MasR axis promotes migration of monocytes/macrophages with a regulatory phenotype to perform phagocytosis and efferocytosis

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