首页> 外文期刊>Clinical and experimental allergy : >Pituitary adenylate cyclase-activating peptide receptor 1 mediates anti-inflammatory effects in allergic airway inflammation in mice.
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Pituitary adenylate cyclase-activating peptide receptor 1 mediates anti-inflammatory effects in allergic airway inflammation in mice.

机译:垂体腺苷酸环化酶激活肽受体1介导小鼠过敏性气道炎症中的抗炎作用。

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BACKGROUND: Bronchial asthma is characterized by airway inflammation and reversible obstruction. Since the gold standard of therapy, a combination of anti-inflammatory corticosteroids and bronchodilatory beta(2) agonists, has recently been discussed to be related to an increased mortality, there is a need for novel therapeutic pathways. OBJECTIVE: A new experimental concept that encompasses the vasoactive intestinal peptide/pituitary adenylate cyclase activating peptide (PACAP) family of receptors by demonstrating the anti-inflammatory effects of the PACAP receptor 1 (PAC1R) in a murine model of allergic asthma is described. METHODS: PAC1R expression was investigated in lung tissue and isolated dendritic cells (DCs) via real-time PCR. Ovalbumin (OVA)-induced asthma models were used in PAC1R-deficient mice and BALB/c mice treated with PAC1R agonist maxadilan (MAX). Bronchoalveolar lavages have been performed and investigated at the cellular and cytokine levels. Fluorescence staining of a frozen lung section has been performed to detect eosinophil granulocytes in lung tissue. Plasma IgE levels have been quantified via the ELISA technique. Lung function was determined using head-out body plethysmography or whole-body plethysmography. RESULTS: Increased PAC1R mRNA expression in lung tissue was present under inflammatory conditions. PAC1R expression was detected on DCs. In OVA-induced asthma models, which were applied to PAC1R-deficient mice (PAC1R(-/-)) and to BALB/c mice treated with the specific PAC1R agonist MAX, PAC1R deficiency resulted in inflammatory effects, while agonistic stimulation resulted in anti-inflammatory effects. No effects on lung function were detected both in the gene-depletion and in the pharmacologic studies. In summary, here, we demonstrate that anti-inflammatory effects can be achieved via PAC1R. CONCLUSION: PAC1R agonists may represent a promising target for an anti-inflammatory therapy in airway diseases such as bronchial asthma.
机译:背景:支气管哮喘的特征是气道炎症和可逆性阻塞。自从治疗的金标准,即抗炎皮质类固醇和支气管扩张性β(2)激动剂的组合最近被讨论与死亡率增加有关,因此需要新的治疗途径。目的:描述一种新的实验概念,其通过在过敏性哮喘小鼠模型中证明PACAP受体1(PAC1R)的抗炎作用,涵盖受体的血管活性肠肽/垂体腺苷酸环化酶激活肽(PACAP)家族。方法:通过实时荧光定量PCR检测肺组织和分离的树突状细胞(DC)中的PAC1R表达。卵清蛋白(OVA)诱导的哮喘模型用于PAC1R缺陷型小鼠和用PAC1R激动剂maxadilan(MAX)治疗的BALB / c小鼠。进行了支气管肺泡灌洗,并在细胞和细胞因子水平上进行了研究。已经进行了冷冻肺切片的荧光染色以检测肺组织中的嗜酸性粒细胞。血浆IgE水平已通过ELISA技术进行了定量。使用抬头身体体积描记法或全身体积描记法确定肺功能。结果:在炎症条件下,肺组织中PAC1R mRNA表达增加。在DC上检测到PAC1R表达。在OVA诱发的哮喘模型中,将其应用于缺乏PAC1R的小鼠(PAC1R(-/-))和经特定PAC1R激动剂MAX治疗的BALB / c小鼠,PAC1R缺乏会导致炎症反应,而激动性刺激则会产生抗炎作用-炎症作用。在基因缺失和药理研究中均未检测到对肺功能的影响。总之,在这里,我们证明可以通过PAC1R实现抗炎作用。结论:PAC1R激动剂可能是气道疾病(如支气管哮喘)抗炎治疗的有希望的靶标。

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