Analysis of NLRP3 in the development of allergic airway disease in mice.

Analysis of NLRP3 in the development of allergic airway disease in mice.
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DOI:
10.4049/jimmunol.1102488
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发表时间:
2012-03-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Ting JP
Ting JP
中科院分区:
其他
文献类型:
--
作者:
Allen IC;Jania CM;Wilson JE;Tekeppe EM;Hua X;Brickey WJ;Kwan M;Koller BH;Tilley SL;Ting JP

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NLRP3是核苷酸结合结构域富含亮氨酸重复序列(NLR)家族的成员之一,目前在过敏性呼吸道疾病的发生发展中的作用仍存在争议。在这里,我们使用多种过敏性哮喘模型来研究NLRP3的生理作用。我们发现,在急性(明胶依赖)和慢性(明胶非依赖)OVA模型中,野生型和Nlrp3-/-小鼠在气道嗜酸性粒细胞增多、组织病理学、粘液产生和气道高反应性方面没有显著差异。除了OVA模型,我们也没有检测到NLRP3在急性或慢性室内尘螨(HDM)抗原暴露引起的过敏性呼吸道疾病的发生中的作用。虽然我们在测试的任何模型中都没有观察到显著的表型差异,但我们确实观察到在没有添加明矾的慢性OVA模型中,Nlrp3/-小鼠与野生型对照相比,IL-13和IL-33显著降低。在所有过敏性呼吸道疾病模型中,肺组织中NLRP3炎症体相关细胞因子IL-1β和IL-18水平均低于检测水平。总而言之,这份报告调查了四种不同的过敏性哮喘模型,并发现NLRP3在无明胶OVA模型中发挥了适度和选定的作用。然而,这种差异并没有很大地改变这种疾病的临床结果。这表明,NLRP3在过敏性哮喘中的作用必须重新评估。
The contribution of NLRP3, a member of the nucleotide-binding domain leucine-rich repeat containing (NLR) family, in the development of allergic airway disease is currently controversial. Here, we used multiple allergic asthma models to examine the physiologic role of NLRP3. We found no significant differences in airway eosinophilia, histopathology, mucus production and airway hyperreactivity between wild type and Nlrp3-/- mice in either acute (alum-dependent) or chronic (alum-independent) OVA models. In addition to the OVA model, we also did not detect a role for NLRP3 in the development of allergic airway disease induced by either acute or chronic house dust mite (HDM) antigen exposure. While we did not observe significant phenotypic differences in any of the models tested, we did observe a significant reduction of IL-13 and IL-33 in Nlrp3-/- mice compared to wild type controls in the chronic OVA model without added alum. In all of the allergic airway disease models, the levels of the NLRP3 inflammasome associated cytokines IL-1β and IL-18 in the lung were below the level of detection. In sum, this report surveyed four different allergic asthma models and found a modest and selected role for NLRP3 in the alum-free OVA model. However this difference did not greatly alter the clinical outcome of the disease. This suggests that the role of NLRP3 in allergic asthma has to be re-evaluated.
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