Protective effect of small molecule analogues of the Acanthocheilonema viteae secreted product ES-62 on oxazolone-induced ear inflammation.
Protective effect of small molecule analogues of the Acanthocheilonema viteae secreted product ES-62 on oxazolone-induced ear inflammation.
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DOI：
10.1016/j.exppara.2015.03.025
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发表时间：
2015-11
影响因子：
2.1
通讯作者：
Harnett W
中科院分区：
文献类型：
--
作者：
Al-Riyami L;Rodgers DT;Rzepecka J;Pineda MA;Suckling CJ;Harnett MM;Harnett W
免疫调节剂ES-62的小分子类似物（sma）已经被生产出来。两种sma可以防止恶唑酮引起的小鼠耳朵皮肤炎症。这种保护作用与减少细胞浸润和胶原沉积有关。保护作用与耳朵中IFNγ mRNA的减少有关。ES-62是啮齿动物棘丝线虫的主要分泌蛋白。该分子含有共价附着的磷酸胆碱（PC）残基，其赋予ES-62抗炎特性，支持基于该活性片段的药物可能对与异常炎症相关的人类疾病具有治疗潜力的观点。在这里，我们证明了ES-62的两种合成小分子类似物（SMA 11a和SMA 12b）在恶唑酮诱导的急性过敏性接触性皮炎小鼠皮肤炎症模型中具有保护作用，通过在恶唑酮致敏前和恶唑酮刺激前给药后耳部炎症显著减少来测量。此外，经测试发现，即使在挑战前首次服用12b，也能有效减少耳部肿胀。耳部组织学分析显示，恶唑酮治疗小鼠的细胞浸润和胶原沉积升高，两种sma治疗均减少了这一现象。同样，恶唑酮诱导的耳部IFNγ mRNA的增加也减少了，但对其他细胞因子的影响没有观察到。最后，没有观察到对耳中肥大细胞群的影响。
Small molecule analogues (SMAs) of the immunomodulator, ES-62, have been produced. Two SMAs protect against oxazolone-induced skin inflammation in mouse ears. Protection is associated with reduced cellular infiltration and collagen deposition. Protection is associated with decreased IFNγ mRNA in the ears. ES-62 is the major secreted protein of the rodent filarial nematode Acanthocheilonema viteae. The molecule contains covalently attached phosphorylcholine (PC) residues, which confer anti-inflammatory properties on ES-62, underpinning the idea that drugs based on this active moiety may have therapeutic potential in human diseases associated with aberrant inflammation. Here we demonstrate that two synthetic small molecule analogues (SMAs) of ES-62 termed SMA 11a and SMA 12b are protective in the oxazolone-induced acute allergic contact dermatitis mouse model of skin inflammation, as measured by a significant reduction in ear inflammation following their administration before oxazolone sensitisation and before oxazolone challenge. Furthermore, it was found that when tested, 12b was effective at reducing ear swelling even when first administered before challenge. Histological analysis of the ears showed elevated cellular infiltration and collagen deposition in oxazolone-treated mice both of which were reduced by treatment with the two SMAs. Likewise, the oxazolone-induced increase in IFNγ mRNA in the ears was reduced but no effect on other cytokines investigated was observed. Finally, no influence on the mast cell populations in the ear was observed.