NF-kappa B/Rel transcription factors: c-Rel promotes airway hyperresponsiveness and allergic pulmonary inflammation.
NF-kappa B/Rel transcription factors: c-Rel promotes airway hyperresponsiveness and allergic pulmonary inflammation.
复制标题
DOI：
10.4049/jimmunol.163.12.6827
复制
发表时间：
1999-12
影响因子：
4.4
通讯作者：
Carolyn E. Donovan;David A. Mark;H. He;H. Liou;Lester Kobzik;Yunsheng Wang;G. T. Sanctis;
中科院分区：
文献类型：
--
作者：
Carolyn E. Donovan;David A. Mark;H. He;H. Liou;Lester Kobzik;Yunsheng Wang;G. T. Sanctis;
转录因子 NF-kappa B/Rel 家族诱导许多参与免疫和炎症反应的基因。个体 NF-kappa B/Rel 亚基种系缺失的小鼠具有不同的表型，表明 NF-kappa B/Rel 转录因子具有不同的功能。我们使用过敏原诱导的肺部炎症和气道高反应性小鼠模型测试了 c-Rel 是否会促进过敏性哮喘。我们的研究重点是 c-Rel，它在淋巴细胞中表达，对淋巴细胞激活很重要。为了应对过敏原致敏和攻击，c-Rel 缺陷小鼠的肺部炎症、支气管肺泡灌洗液嗜酸性粒细胞增多或血清总 IgE 并未增加。 c-Rel 缺乏也阻止了气道高反应性的诱导。经过敏原处理的野生型小鼠与 NF-κ B 共有位点的 DNA 结合增加。经过敏原处理的 c-Rel 缺陷小鼠中趋化因子表达发生改变。与野生型对照相比，经过敏原处理的 c-Rel 缺陷小鼠中受 NF-kappa B 调节的单核细胞趋化蛋白-1 减少。野生型小鼠中过敏原攻击后 NF-kappa B/Rel 转录因子的增加以及 c-Rel 缺陷小鼠中过敏原反应性的降低表明 c-Rel 促进过敏性炎症。 c-Rel 缺陷小鼠肺部趋化因子表达的改变可能会抑制过敏原诱导的肺部炎症和气道高反应性。
The NF-kappa B/Rel family of transcription factors induces many genes involved in immune and inflammatory responses. Mice with germline deletions of individual NF-kappa B/Rel subunits have different phenotypes, suggesting that the NF-kappa B/Rel transcription factors have different functions. We tested whether c-Rel promotes allergic asthma using a murine model of allergen-induced pulmonary inflammation and airway hyperresponsiveness. Our investigation focused on c-Rel, which is expressed in lymphoid cells and is important for lymphocyte activation. In response to allergen sensitization and challenge, c-Rel-deficient mice did not develop increases in pulmonary inflammation, bronchoalveolar lavage fluid eosinophilia, or total serum IgE. c-Rel deficiency also prevented the induction of airway hyperresponsiveness. Allergen-treated wild-type mice had increased DNA binding to an NF-kappa B consensus site. Chemokine expression was altered in allergen-treated c-Rel-deficient mice. Monocyte chemoattractant protein-1, which is regulated by NF-kappa B, was decreased in allergen-treated c-Rel-deficient mice relative to wild-type controls. The increase in NF-kappa B/Rel transcription factors after allergen challenge in wild-type mice and the decrease in allergen reactivity found in c-Rel-deficient mice indicate that c-Rel promotes allergic inflammation. Alteration of pulmonary chemokine expression in c-Rel-deficient mice may inhibit allergen-induced pulmonary inflammation and airway hyperresponsiveness.