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聚肌苷酸:聚胞苷酸通过增加胸腺基质淋巴细胞生成素的表达加重小鼠中卡泊三醇诱导的特应性皮炎样皮肤损伤。

Polyinosinic:polycytidylic acid aggravates calcipotriol-induced atopic dermatitis-like skin lesions in mice by increasing the expression of thymic stromal lymphopoietin.

作者信息

Wan Haoyue, Yang Huixue, Wei Mingjing, Chen Wenqi

机构信息

Department of Dermatology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

出版信息

Ann Transl Med. 2022 Feb;10(4):209. doi: 10.21037/atm-22-282.

DOI:10.21037/atm-22-282
PMID:35280398
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8908153/
Abstract

BACKGROUND

Polyinosinic:polycytidylic acid [poly (I:C)] is a synthetic viral double-stranded RNA analog that can activate Toll-like receptor 3 (TLR3) and induce the release of thymic stromal lymphopoietin (TSLP). TSLP has been shown to contribute to atopic dermatitis (AD). This study explored the effects of poly (I:C) in a calcipotriol-induced model of murine AD.

METHODS

Calcipotriol (MC903) was used to establish AD-like mice model. Mice in the MC903 + poly (I:C) group were then treated with poly (I:C) in a concentration of 5 µg/g bodyweight. The impact of poly (I:C) treatment on these animals was assessed based upon changes in lesions, bodyweight, ear thickness, and histopathological findings. In addition, serum interleukin 4 (IL-4), interferon-γ (IFN-γ), immunoglobulin E (IgE), IL-13, and TSLP levels were measured using enzyme-linked immunosorbent assay (ELISA), while tissue IL-13 and TSLP levels were assessed using ELISA, Western blotting, and immunohistochemical staining, and mast cell infiltration was assessed through toluidine blue (TBO) staining.

RESULTS

Relative to vehicle control treatment, poly (I:C) administration was associated with a significant exacerbation of calcipotriol-induced AD-like murine skin lesions. In animals treated with poly (I:C), the levels of serum IL-4, IL-13 and TSLP increased significantly, while the level of IFN-γ did not change. It also increased IL-13 and TSLP levels in skin lesions relative to the control-group mice and increased dermal mast cell infiltration and IgE production.

CONCLUSIONS

These data indicate that poly (I:C) treatment and exogenous activation of TLR3 exacerbate murine calcipotriol-induced AD-like skin lesions in part by increasing the production of TSLP and other T-helper 2 (Th2)-related cytokines.

KEYWORDS

Atopic dermatitis (AD); polyinosinic:polycytidylic acid [poly (I:C)]; thymic stromal lymphopoietin (TSLP); Toll-like receptor 3 (TLR3).

摘要

背景

聚肌苷酸:聚胞苷酸[聚（I:C）]是一种合成的病毒双链RNA类似物，可激活Toll样受体3（TLR3）并诱导胸腺基质淋巴细胞生成素（TSLP）的释放。TSLP已被证明与特应性皮炎（AD）有关。本研究探讨了聚（I:C）在钙泊三醇诱导的小鼠AD模型中的作用。

方法

使用钙泊三醇（MC903）建立AD样小鼠模型。然后，对MC903 +聚（I:C）组的小鼠以5μg/g体重的浓度给予聚（I:C）。根据病变、体重、耳厚度和组织病理学结果的变化评估聚（I:C）治疗对这些动物的影响。此外，使用酶联免疫吸附测定（ELISA）测量血清白细胞介素4（IL-4）、干扰素-γ（IFN-γ）、免疫球蛋白E（IgE）、IL-13和TSLP水平，而使用ELISA、蛋白质印迹和免疫组织化学染色评估组织IL-13和TSLP水平，并通过甲苯胺蓝（TBO）染色评估肥大细胞浸润。

结果

相对于载体对照治疗，给予聚（I:C）与钙泊三醇诱导的AD样小鼠皮肤病变的显著加重相关。在用聚（I:C）治疗的动物中，血清IL-4、IL-13和TSLP水平显著升高，而IFN-γ水平未改变。相对于对照组小鼠，它还增加了皮肤病变中的IL-13和TSLP水平，并增加了真皮肥大细胞浸润和IgE产生。

结论

这些数据表明，聚（I:C）治疗和TLR3的外源性激活部分通过增加TSLP和其他辅助性T细胞2（Th2）相关细胞因子的产生来加重小鼠钙泊三醇诱导的AD样皮肤病变。

关键词

特应性皮炎（AD）；聚肌苷酸:聚胞苷酸[聚（I:C）]；胸腺基质淋巴细胞生成素（TSLP）；Toll样受体3（TLR3）

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4373/8908153/500311985ab0/atm-10-04-209-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4373/8908153/ef26c3e19571/atm-10-04-209-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4373/8908153/82982dcf88e5/atm-10-04-209-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4373/8908153/3f45f19676a8/atm-10-04-209-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4373/8908153/ad297284c52b/atm-10-04-209-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4373/8908153/500311985ab0/atm-10-04-209-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4373/8908153/ef26c3e19571/atm-10-04-209-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4373/8908153/82982dcf88e5/atm-10-04-209-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4373/8908153/3f45f19676a8/atm-10-04-209-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4373/8908153/ad297284c52b/atm-10-04-209-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4373/8908153/500311985ab0/atm-10-04-209-f5.jpg

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