Impaired induction of allergic lung inflammation by Alternaria alternata mutant MAPK homologue Fus3.
Impaired induction of allergic lung inflammation by Alternaria alternata mutant MAPK homologue Fus3.
复制标题
DOI：
10.3109/01902148.2013.835009
复制
发表时间：
2013-11
影响因子：
1.7
通讯作者：
Doherty TA
中科院分区：
文献类型：
--
作者：
Kim HK;Baum R;Lund S;Khorram N;Yang SL;Chung KR;Doherty TA
真菌过敏原链格孢与哮喘的发生有关，尽管链格孢的致敏性机制在很大程度上是未知的。本研究的目的是确定是否链格孢属的MAP激酶同源物Fus 3有助于过敏性气道反应。将野生型（WT）和Fus 3缺陷型链格孢属提取物鼻内给予小鼠。还施用来自引入了Fus 3的功能性拷贝的Fus 3缺陷链格孢属的提取物（CpFus 3）。对小鼠进行一次攻击，并评估BAL嗜酸性粒细胞和先天性细胞因子IL-33、胸腺基质淋巴细胞生成素（TSLP）和IL-25（IL-17 E）的水平。链格孢属提取物或蛋白酶抑制提取物与（OVA）在致敏过程中之前，卵清蛋白唯一的挑战，以确定提取物的佐剂活性。检测BAL炎性细胞、Th 2细胞因子和表达OX 40的Th 2细胞的水平以及气道浸润和粘液产生。WT链格孢在3天内诱导先天性气道嗜酸性粒细胞增多。给予Fus 3缺陷链格孢菌的小鼠在发展气道嗜酸性粒细胞增多症方面显著受损，而气道嗜酸性粒细胞增多症在很大程度上被CpFus 3恢复。此外，与WT和CpFus 3提取物相比，用Fus 3突变体提取物激发后BAL IL-33、TSLP和嗜酸性粒细胞趋化因子-1水平降低。WT和CpFus 3提取物在体内表现出很强的佐剂活性，因为诱导了BAL嗜酸性粒细胞、Th 2细胞因子和表达OX 40的Th 2细胞的水平以及支气管周围炎症和粘液产生。相反，Fus 3提取物或蛋白酶抑制WT提取物的佐剂活性大大受损。最后，Fus 3突变体提取物中的蛋白酶活性和Alt a1水平降低。因此，Fus 3有助于链格孢属的Th 2-敏化特性。
The fungal allergen Alternaria alternata is associated with development of asthma, though the mechanisms underlying the allergenicity of Alternaria are largely unknown. The aim of this study was to identify whether the MAP kinase homologue Fus3 of Alternaria contributed to allergic airway responses. Wild-type (WT) and Fus3 deficient Alternaria extracts were given intranasal to mice. Extracts from Fus3 deficient Alternaria that had a functional copy of Fus3 introduced were also administered (CpFus3). Mice were challenged once and levels of BAL eosinophils and innate cytokines IL-33, thymic stromal lymphopoeitin (TSLP), and IL-25 (IL-17E) were assessed. Alternaria extracts or protease-inhibited extract were administered with (OVA) during sensitization prior to ovalbumin only challenges to determine extract adjuvant activity. Levels of BAL inflammatory cells, Th2 cytokines, and OX40-expressing Th2 cells as well as airway infiltration and mucus production were measured. WT Alternaria induced innate airway eosinophilia within 3 days. Mice given Fus3 deficient Alternaria were signifcantly impaired in developing airway eosinophilia that was largely restored by CpFus3. Further, BAL IL-33, TSLP, and Eotaxin-1 levels were reduced after challenge with Fus3 mutant extract compared with WT and CpFus3 extracts. WT and CpFus3 extracts demonstrated strong adjuvant activity in vivo as levels of BAL eosinophils, Th2 cytokines, and OX40-expressing Th2 cells as well as peribronchial inflammation and mucus production were induced. In contrast, the adjuvant activity of Fus3 extract or protease-inhibited WT extract was largely impaired. Finally, protease activity and Alt a1 levels were reduced in Fus3 mutant extract. Thus, Fus3 contributes to the Th2-sensitizing properties of Alternaria.
登录
查看更多内容
蛋白酶激活的受体2激活髓样树突状细胞可调节过敏性气道炎症。
影响因子：
5.8
作者：
Lewkowich IP;Day SB;Ledford JR;Zhou P;Dienger K;Wills-Karp M;Page K
通讯作者：
Page K
DOI：
10.4049/jimmunol.1101632
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Doherty TA;Khorram N;Sugimoto K;Sheppard D;Rosenthal P;Cho JY;Pham A;Miller M;Croft M;Broide DH
通讯作者：
Broide DH
影响因子：
14.2
作者：
Chruszcz, Maksymilian;Chapman, Martin D.;Osinski, Tomasz;Solberg, Robert;Demas, Matthew;Porebski, Przemyslaw J.;Majorek, Karolina A.;Pomes, Anna;Minor, Wladek
通讯作者：
Minor, Wladek
影响因子：
14.2
作者：
Pulimood, Thomas B.;Corden, Julie M.;Nasser, Shuaib M.
通讯作者：
Nasser, Shuaib M.
影响因子：
14.2
作者：
Green, BJ;Sercombe, JK;Tovey, ER
通讯作者：
Tovey, ER