Excision release of 5?hydroxycytosine oxidatively induced DNA base lesions from the lung genome by cat dander extract challenge stimulates allergic airway inflammation.
Excision release of 5?hydroxycytosine oxidatively induced DNA base lesions from the lung genome by cat dander extract challenge stimulates allergic airway inflammation.
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DOI：
10.1111/cea.13284
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Sur S
中科院分区：
文献类型：
--
作者：
Hosoki K;Jaruga P;Itazawa T;Aguilera-Aguirre L;Coskun E;Hazra TK;Boldogh I;Dizdaroglu M;Sur S
豚草花粉提取物(RWPE)诱导TLR4-NFicB-CXCL依赖于TLR4-NFicB-CXCL将产生ROS的中性粒细胞重新聚集到呼吸道，并依赖于OGG1DNA糖解酶从氧化诱导的8-OH-Gua DNA碱基损伤的呼吸道上皮细胞基因组中切除损伤。给予游离8-羟基瓜胶碱刺激RWPE诱导的过敏性肺部炎症。这些研究表明，过敏原提取物对先天受体及其适配器的刺激，启动了一系列DNA碱基损伤的切除，从而促进了先天/过敏性肺部炎症。为了验证这样一种假设，即过敏原提取物刺激保守的固有受体/适配器途径会导致肺基因组中一组致炎氧化诱导的DNA碱基损伤被切除，从而刺激过敏性呼吸道炎症。给野生型(WT)、Tlr4KO、Tlr2KO、Myd88KO和TrifKO小鼠一次或多次鼻腔注射猫皮屑提取物(CDE)，并对其先天或变态反应性炎症和基因表达进行定量。我们利用GC-MS/MS对CDE攻击幼龄小鼠后一组氧化诱导的DNA碱基损伤进行了定量。一次CDE刺激刺激部分依赖TLR4和TLR2，完全依赖MyD88，但不依赖TRIF的先天中性粒细胞募集。一次CDE攻击刺激依赖于MyD88的DNA碱基损伤从肺基因组中切除5-OH-Cyt、FapyAde和FapyGua。用5-OH-Cyt对幼稚的WT小鼠进行一次挑战，就能刺激中性粒细胞肺部炎症。多次滴注CDE可刺激MyD88依赖的过敏性呼吸道炎症。5-OH-Cyt与CDE联合多次给药可刺激变态反应性致敏和过敏性呼吸道炎症。我们首次展示了CDE挑战刺激依赖于MyD88的DNA碱基损伤的切除。我们的数据表明，生成的游离碱(S)参与了CDE诱导的先天/过敏性肺部炎症。我们认为，用特异性的抑制剂阻断呼吸道中的MyD88通路可能是一种新的靶向策略，通过氧化诱导DNA碱基损伤来抑制变态反应性疾病中先天和获得性免疫炎症的放大。
Ragweed pollen extract (RWPE) induces TLR4-NFicB-CXCL-dependent recruitment of ROS-generating neutrophils to the airway and OGG1 DNA glycosy-lase-dependent excision of oxidatively induced 8-OH-Gua DNA base lesions from the airway epithelial cell genome. Administration of free 8-OH-Gua base stimulates RWPE-induced allergic lung inflammation. These studies suggest that stimulation of innate receptors and their adaptor by allergenic extracts initiates excision of a set of DNA base lesions that facilitate innate/allergic lung inflammation. To test the hypothesis that stimulation of a conserved innate receptor/ adaptor pathway by allergenic extracts induces excision of a set of pro-inflammatory oxidatively induced DNA base lesions from the lung genome that stimulate allergic airway inflammation. Wild-type (WT), Tlr4KO, Tlr2KO, Myd88KO, and TrifKO mice were intra-nasally challenged once or repeatedly with cat dander extract (CDE), and innate or allergic inflammation and gene expression were quantified. We utilized GC-MS/MS to quantify a set of oxidatively induced DNA base lesions after challenge of naïve mice with CDE. A single CDE challenge stimulated innate neutrophil recruitment that was partially dependent on TLR4 and TLR2, and completely on Myd88, but not TRIF. A single CDE challenge stimulated MyD88-dependent excision of DNA base lesions 5-OH-Cyt, FapyAde, and FapyGua from the lung genome. A single challenge of naïve WT mice with 5-OH-Cyt stimulated neutrophilic lung inflammation. Multiple CDE instillations stimulated MyD88-dependent allergic airway inflammation. Multiple administrations of 5-OH-Cyt with CDE stimulated allergic sensitization and allergic airway inflammation. We show for the first time that CDE challenge stimulates MyD88-dependent excision of DNA base lesions. Our data suggest that the resultant-free base(s) contribute to CDE-induced innate/allergic lung inflammation. We suggest that blocking the MyD88 pathway in the airways with specific inhibitors may be a novel targeted strategy of inhibiting amplification of innate and adaptive immune inflammation in allergic diseases by oxidatively induced DNA base lesions.
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影响因子：
32.4
作者：
Kawai, T;Adachi, O;Akira, S
通讯作者：
Akira, S
由8-氧气的DNA糖基酶-1-kRAS-NF-κB途径引起的先天炎症。
DOI：
10.4049/jimmunol.1401625
发表时间：
2014-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Aguilera-Aguirre L;Bacsi A;Radak Z;Hazra TK;Mitra S;Sur S;Brasier AR;Ba X;Boldogh I
通讯作者：
Boldogh I
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
12.4
作者：
Linneberg, A;Nielsen, NH;Jorgensen, T
通讯作者：
Jorgensen, T
影响因子：
3.8
作者：
Hazra, Tapas K.;Das, Aditi;Roy, Rabindra
通讯作者：
Roy, Rabindra