Protection against lung pathology during obesity-accelerated ageing in mice by the parasitic worm product ES-62.
Protection against lung pathology during obesity-accelerated ageing in mice by the parasitic worm product ES-62.
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DOI：
10.3389/fimmu.2023.1285069
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
随着年龄的增长，小鼠的肺部会发生病变，高卡路里饮食(HCD)可能会加速这一过程。ES-62是一种由寄生蠕虫Acanthocheilonema viteae分泌的蛋白，通过共价连接的磷胆碱(PC)部分具有免疫调节作用。在这项研究中，我们发现，从10周龄开始，用ES-62每周治疗C57BL/6J小鼠可以保护雄性小鼠而不是雌性小鼠免受肺部病理的影响，表现为细胞渗透和呼吸道重塑减少，尤其是160天龄以下的小鼠。ES-62还降低了雄性小鼠肺部细胞因子IL-4和IL-17以及TLR/IL-1R接头MyD88的基因表达，尽管HCD诱导的这些炎症标志物的增加直到340至500天才被检测到。两种药物样的ES-62 PC小分子类似物(SMA)的组合在肺病理和炎症标志物方面对雄性小鼠的肺部产生了大致相似的保护作用，此外还减少了HCD诱导的IL-5的表达。总体而言，我们的数据显示，ES-62及其SMA可提供保护，防止HCD在衰老过程中加速肺部病变。鉴于Th2型细胞因子和IL-17的靶向性，我们在ES-62的背景下讨论了这种保护作用。S之前曾描述过改善哮喘小鼠模型的呼吸道高反应性。
Mice develop pathology in the lungs as they age and this may be accelerated by a high calorie diet (HCD). ES-62 is a protein secreted by the parasitic worm Acanthocheilonema viteae that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties. In this study, we show that weekly treatment of C57BL/6J mice with ES-62 protected against pathology in the lungs in male but not female mice fed a HCD from 10 weeks of age as shown by reductions in cellular infiltration and airway remodelling, particularly up to 160 days of age. ES-62 also reduced gene expression of the cytokines IL-4 and IL-17 and in addition the TLR/IL-1R adaptor MyD88, in the lungs of male mice although HCD-induced increases in these inflammatory markers were not detected until between 340 and 500 days of age. A combination of two drug-like ES-62 PC-based small molecule analogues (SMAs), produced broadly similar protective effects in the lungs of male mice with respect to both lung pathology and inflammatory markers, in addition to a decrease in HCD-induced IL-5 expression. Overall, our data show that ES-62 and its SMAs offer protection against HCD-accelerated pathological changes in the lungs during ageing. Given the targeting of Th2 cytokines and IL-17, we discuss this protection in the context of ES-62’s previously described amelioration of airway hyper-responsiveness in mouse models of asthma.
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影响因子：
4.6
作者：
Coltherd JC;Rodgers DT;Lawrie RE;Al-Riyami L;Suckling CJ;Harnett W;Harnett MM
通讯作者：
Harnett MM
影响因子：
7.3
作者：
Al-Riyami L;Pineda MA;Rzepecka J;Huggan JK;Khalaf AI;Suckling CJ;Scott FJ;Rodgers DT;Harnett MM;Harnett W
通讯作者：
Harnett W
DOI：
10.3390/molecules23102669
发表时间：
2018-10-17
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Doonan J;Thomas D;Wong MH;Ramage HJ;Al-Riyami L;Lumb FE;Bell KS;Fairlie-Clarke KJ;Suckling CJ;Michelsen KS;Jiang HR;Cooke A;Harnett MM;Harnett W
通讯作者：
Harnett W
影响因子：
1.5
作者：
Lumb, Felicity E.;Crowe, Jenny;Harnett, William
通讯作者：
Harnett, William
影响因子：
--
作者：
Pineda, Miguel A.;McGrath, Mairi A.;Harnett, Margaret M.
通讯作者：
Harnett, Margaret M.