PDF(Pubmed)
Abstract：
The anti-inflammatory effect of an α7nAChR agonist, PNU-282987, has previously been explored in the context of inflammatory disease. However, the effects of PNU-282987 on type 2 innate lymphoid cells (ILC2s)-mediated allergic airway inflammation has not yet been established.
To determine the effects of PNU-282987 on the function of ILC2s in the context of IL-33- or Alternaria Alternata (AA)- induced airway inflammation.
PNU-282987 was administered to mice that received recombinant IL-33 or AA intranasal challenges. Lung histological analysis and flow cytometry were performed to determine airway inflammation and the infiltration and activation of ILC2s. The previously published α7nAChR agonist GTS-21 was employed as a comparable reagent. ILC2s were isolated from murine lung tissue and cultured in vitro in the presence of IL-33, IL-2, and IL-7 with/without either PNU-282987 or GTS-21. The expression of the transcription factors GATA3, IKK, and NF-κB were also determined.
PNU-282987 and GTS-21 significantly reduced goblet cell hyperplasia in the airway, eosinophil infiltration, and ILC2s numbers in BALF, following IL-33 or AA challenge. In vitro IL-33 stimulation of isolated lung ILC2s showed a reduction of GATA3 and Ki67 in response to PNU-282987 or GTS-21 treatments. There was a significant reduction in IKK and NF-κB phosphorylation in the PNU-282987-treated group when compared to the GTS-21-treated ILC2s.
PNU-282987 inhibits ILC2-associated airway inflammation, where its effects were comparable to that of GTS-21.
To determine the effects of PNU-282987 on the function of ILC2s in the context of IL-33- or Alternaria Alternata (AA)- induced airway inflammation.
PNU-282987 was administered to mice that received recombinant IL-33 or AA intranasal challenges. Lung histological analysis and flow cytometry were performed to determine airway inflammation and the infiltration and activation of ILC2s. The previously published α7nAChR agonist GTS-21 was employed as a comparable reagent. ILC2s were isolated from murine lung tissue and cultured in vitro in the presence of IL-33, IL-2, and IL-7 with/without either PNU-282987 or GTS-21. The expression of the transcription factors GATA3, IKK, and NF-κB were also determined.
PNU-282987 and GTS-21 significantly reduced goblet cell hyperplasia in the airway, eosinophil infiltration, and ILC2s numbers in BALF, following IL-33 or AA challenge. In vitro IL-33 stimulation of isolated lung ILC2s showed a reduction of GATA3 and Ki67 in response to PNU-282987 or GTS-21 treatments. There was a significant reduction in IKK and NF-κB phosphorylation in the PNU-282987-treated group when compared to the GTS-21-treated ILC2s.
PNU-282987 inhibits ILC2-associated airway inflammation, where its effects were comparable to that of GTS-21.
摘要：
α7nAChR激动剂的抗炎作用，PNU-282987先前已在炎性疾病的背景下进行了探索。然而,PNU-282987对2型先天淋巴细胞(ILC2s)介导的过敏性气道炎症的作用尚未确定.
确定PNU-282987在IL-33或链格孢菌（AA）诱导的气道炎症中对ILC2s功能的影响。
将PNU-282987给予接受重组IL-33或AA鼻内攻击的小鼠。进行肺组织学分析和流式细胞术以确定气道炎症以及ILC2s的浸润和激活。先前公开的α7nAChR激动剂GTS-21用作可比较的试剂。从小鼠肺组织中分离ILC2s,并在有/没有PNU-282987或GTS-21的IL-33、IL-2和IL-7存在下体外培养。转录因子GATA3、IKK、和NF-κB也被测定。
PNU-282987和GTS-21显著减少气道杯状细胞增生，嗜酸性粒细胞浸润,和BALF中的ILC2号，在IL-33或AA攻击后。对分离的肺ILC2s的体外IL-33刺激显示响应于PNU-282987或GTS-21治疗的GATA3和Ki67减少。与GTS-21处理的ILC2s相比，PNU-282987处理组的IKK和NF-κB磷酸化显着降低。
PNU-282987抑制ILC2相关气道炎症，其效果与GTS-21相当。
确定PNU-282987在IL-33或链格孢菌（AA）诱导的气道炎症中对ILC2s功能的影响。
将PNU-282987给予接受重组IL-33或AA鼻内攻击的小鼠。进行肺组织学分析和流式细胞术以确定气道炎症以及ILC2s的浸润和激活。先前公开的α7nAChR激动剂GTS-21用作可比较的试剂。从小鼠肺组织中分离ILC2s,并在有/没有PNU-282987或GTS-21的IL-33、IL-2和IL-7存在下体外培养。转录因子GATA3、IKK、和NF-κB也被测定。
PNU-282987和GTS-21显著减少气道杯状细胞增生，嗜酸性粒细胞浸润,和BALF中的ILC2号，在IL-33或AA攻击后。对分离的肺ILC2s的体外IL-33刺激显示响应于PNU-282987或GTS-21治疗的GATA3和Ki67减少。与GTS-21处理的ILC2s相比，PNU-282987处理组的IKK和NF-κB磷酸化显着降低。
PNU-282987抑制ILC2相关气道炎症，其效果与GTS-21相当。
