Angiotensin‐(1–7) inhibits allergic inflammation, via the MAS1 receptor, through suppression of ERK1/2‐ and NF‐κB‐dependent pathways

El-Hashim, Ahmed Z.; Renno, Waleed M.; Raghupathy, Raj; Abduo, Heba; Akhtar, Saghir; Benter, İbrahim F.

doi:10.1111/j.1476-5381.2012.01905.x

Cited by 144 publications

(130 citation statements)

References 42 publications

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“…22 Treatment with Ang-(1-7) alleviated inflammation via regulation of the extracellular signal regulated kinase, one of the MAPK family members, and NF-jB pathways in an allergic asthma mouse model. 67 In line with our previous studies, activation of the ACE2/Ang-(1-7)/Mas axis downregulated phosphorylation of MAPKs and NF-jB signaling. 33,36 These data indicated that ACE2 may ameliorate the inflammatory response by regulating MAPKs and NF-jB pathways.…”

Section: Ace2 Reduces Ab-induced Inflammation In Human Rpesupporting

confidence: 76%

Overexpression of Angiotensin-Converting Enzyme 2 Ameliorates Amyloid β-Induced Inflammatory Response in Human Primary Retinal Pigment Epithelium

Lin

Qiu

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Overexpression of angiotensin-converting enzyme 2 ameliorates amyloid b-induced inflammatory response in human primary retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2017;58:3018-3028. DOI:10.1167/ iovs.17-21546 PURPOSE. Amyloid-b (Ab) is a major constituent of drusen, which is a hallmark of early AMD. The purpose of this study was to investigate whether enhancement of ACE2, an important component of the protective angiotensin-converting enzyme 2 (ACE2)/Ang-(1-7)/Mas axis of the renin angiotensin system (RAS), ameliorates Ab-induced inflammatory response in human RPE cells. METHODS.Annexin-V FITC/propidium iodide assay for detecting apoptosis rate was used to determine the optimum concentration and incubation time of Ab1-42. ACE2 plasmid was transfected into primary cultured human RPE (hRPE) and ARPE-19 cells for 6 hours followed by stimulation with Ab1-42 at the concentration of 1 lM for 48 hours. Gene expression was detected by real-time PCR and protein levels were determined by Western blotting or ELISA. A779, an antagonist of Ang-(1-7), was used to further confirm the involvement of ACE2/Ang-(1-7)/Mas axis. RESULTS.Flow cytometry showed that the optimal concentration of Ab1-42 was 1 lM and the optimal incubation time was 48 hours. Ab1-42 upregulated the expression of IL-1b and monocyte chemoattractant protein-1. ACE2 plasmid significantly upregulated the expression of ACE2 and Ang-(1-7) in hRPE and ARPE-19 cells. Activation of ACE2 reduced the overproduction of inflammatory cytokines at both mRNA and protein levels in hRPE and ARPE-19 cells stimulated with Ab1-42. Furthermore, an antagonist of Ang-(1-7), A779 reversed the anti-inflammatory effect of ACE2.CONCLUSIONS. Overexpression of ACE2 ameliorates Ab-induced inflammatory response by activating the ACE2/Ang-(1-7)/Mas axis in human RPE cells. Our data suggest that ACE2/Ang-(1-7)/Mas axis may be a promising target for developing novel therapies for inflammation response in AMD.

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Section: Ace2 Reduces Ab-induced Inflammation In Human Rpesupporting

confidence: 76%

Overexpression of Angiotensin-Converting Enzyme 2 Ameliorates Amyloid β-Induced Inflammatory Response in Human Primary Retinal Pigment Epithelium

Lin

Qiu

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Therefore, the increase of antigen-presenting cell migration into atherosclerotic plaques as well as the enhanced plaque size, which we observed in our ApoEKO mouse model, may be mediated by an effect of Mas on chemokine expression. Well in line with this observation, Mas deficiency enhances the expression of the chemokine CCL2 in vitro and in vivo with NF-κB as a key regulator (30,31).…”

Section: Discussionmentioning

confidence: 66%

Role of the receptor Mas in macrophage-mediated inflammation in vivo

Hammer

Yang

Friedrich

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Recently, an alternative renin–angiotensin system pathway has been described, which involves binding of angiotensin-(1–7) to its receptor Mas. The Mas axis may counterbalance angiotensin-II–mediated proinflammatory effects, likely by affecting macrophage function. Here we investigate the role of Mas in murine models of autoimmune neuroinflammation and atherosclerosis, which both involve macrophage-driven pathomechanisms. Mas signaling affected macrophage polarization, migration, and macrophage-mediated T-cell activation. Mas deficiency exacerbated the course of experimental autoimmune encephalomyelitis and increased macrophage infiltration as well as proinflammatory gene expression in the spleen and spinal cord. Furthermore, Mas deficiency promoted atherosclerosis by affecting macrophage infiltration and migration and led to increased oxidative stress as well as impaired endothelial function in ApoE-deficient mice. In summary, we identified the Mas axis as an important factor in macrophage function during inflammation of the central nervous and vascular system in vivo. Modulating the Mas axis may constitute an interesting therapeutic target in multiple sclerosis and/or atherosclerosis.

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“…5 μm thick sections were stained with hematoxylin and eosin (H & E) and examined for pathological changes under light microscopy (El-Hashim et al, 2012).…”

Section: Airway and Heart Histologymentioning

confidence: 99%

Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model

Dhawale

Amara

Karpe

et al. 2016

Toxicology and Applied Pharmacology

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Angiotensin‐(1–7) inhibits allergic inflammation, via the MAS1 receptor, through suppression of ERK1/2‐ and NF‐κB‐dependent pathways

Cited by 144 publications

References 42 publications

Overexpression of Angiotensin-Converting Enzyme 2 Ameliorates Amyloid β-Induced Inflammatory Response in Human Primary Retinal Pigment Epithelium

Overexpression of Angiotensin-Converting Enzyme 2 Ameliorates Amyloid β-Induced Inflammatory Response in Human Primary Retinal Pigment Epithelium

Role of the receptor Mas in macrophage-mediated inflammation in vivo

Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model

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