Angiotensin-(1-7) inhibits allergic inflammation, via the MAS1 receptor, through suppression of ERK1/2- and NF-κB-dependent pathways
Angiotensin-(1-7) inhibits allergic inflammation, via the MAS1 receptor, through suppression of ERK1/2- and NF-κB-dependent pathways
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DOI：
10.1111/j.1476-5381.2012.01905.x
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发表时间：
2012-07-01
影响因子：
7.3
通讯作者：
Benter, Ibrahim F.
中科院分区：
文献类型：
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作者：
El-Hashim, Ahmed Z.;Renno, Waleed M.;Benter, Ibrahim F.
背景与目的血管紧张素-（17）[Ang-（17）]在心血管疾病和关节炎模型中具有抗炎作用，但其在哮喘中的作用尚不清楚。我们研究了Ang-（17）是否在哮喘小鼠模型中具有抗炎作用。实验方法在卵白蛋白激发的过敏性哮喘小鼠模型中，在4天的时间内评价单独使用Ang-（17）或与MAS 1受体拮抗剂A779联合使用的作用。在第5天，进行支气管肺泡灌洗，将肺切片并进行组织学评估，以定量杯状细胞、血管周围和支气管周围炎症和纤维化。促炎性ERK 1/2和I？B-A已评估。此外，还观察了Ang-（17）对人外周血单个核细胞（HPBMC）增殖的影响。关键结果Ang-（17）减弱卵清蛋白诱导的总细胞计数、嗜酸性粒细胞、淋巴细胞和中性粒细胞的增加。Ang-（17）还可减少卵清蛋白诱导的血管周围和支气管周围炎症、纤维化和杯状细胞增生/化生。此外，Ang-（17）还能降低卵清蛋白诱导的ERK 1/2和I？B-A。Ang-（17）的这些作用可被MAS 1受体拮抗剂A779逆转。此外，Ang-（17）抑制植物血凝素（PHA）诱导的HPBMC增殖。结论：Ang-（17）通过其MAS 1受体参与了过敏性哮喘的抗炎作用，提示激活MAS 1受体可能是哮喘治疗的新途径。
BACKGROUND AND PURPOSE Angiotensin-(17) [Ang-(17)] has anti-inflammatory effects in models of cardiovascular disease and arthritis, but its effects in asthma are unknown. We investigated whether Ang-(17) has anti-inflammatory actions in a murine model of asthma. EXPERIMENTAL APPROACH The effects of Ang-(17) alone or in combination with the MAS1 receptor antagonist, A779, were evaluated over a 4 day period in an ovalbumin-challenged mouse model of allergic asthma. On day 5, bronchoalveolar lavage was performed, and lungs were sectioned and assessed histologically for quantification of goblet cells, perivascular and peribronchial inflammation and fibrosis. Biochemical analysis of the pro-inflammatory ERK1/2 and I?B-a was assessed. In addition, the effect of Ang-(17) on proliferation of human peripheral blood mononuclear cells (HPBMC) was investigated. KEY RESULTS Ang-(17) attenuated ovalbumin-induced increases in total cell counts, eosinophils, lymphocytes and neutrophils. Ang-(17) also decreased the ovalbumin-induced perivascular and peribronchial inflammation, fibrosis and goblet cell hyper/metaplasia. Additionally, Ang-(17) reduced the ovalbumin-induced increase in the phosphorylation of ERK1/2 and I?B-a. These effects of Ang-(17) were reversed by the MAS1 receptor antagonist A779. Furthermore, Ang-(17) inhibited phytohaemagglutinin (PHA)-induced HPBMC proliferation. CONCLUSION AND IMPLICATIONS Ang-(17), via its MAS1 receptor, acts as an anti-inflammatory pathway in allergic asthma, implying that activation of the MAS1 receptor may represent a novel approach to asthma therapy.