Anti-Inflammatory Effects of Polyglycerol Sulfates and Natural Polyanions in Type 2 Inflammation

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2025-06-09 DOI:10.1021/acs.biomac.5c00420

Clemens Krage , Peyman Malek Mohammadi Nouri , Jens Dernedde , Jayachandran N. Kizhakkedathu , Sarah Hedtrich , Rainer Haag , Katharina Achazi

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Abstract

Type 2 inflammation is an essential defense mechanism of the innate and adaptive immune systems, but when dysregulated, it can cause chronic atopic diseases like allergic asthma and atopic dermatitis. Thymic stromal lymphopoietin (TSLP) helps drive type 2 inflammation by guiding T cells toward a type 2 helper cell (T_H2) subtype and stimulating B cells’ antibody production. Fibronectin (FN) has recently been found at elevated levels in the plasma of children with atopic dermatitis and shown a potential proinflammatory role in bronchial epithelium tissue models. Both proteins’ surface charges suggest potential interaction with charged molecules. Seeking new strategies against type 2 inflammation, we found that negatively charged polyglycerol sulfates strongly bind to TSLP and FN. We confirmed that these molecules inhibit inflammation by reducing the TSLP-mediated type 2 polarization of CD4⁺ T cells. We found that adding polyglycerol sulfate to FN-triggered inflamed bronchial epithelium models reduced TSLP expression and interleukin 6 secretion.

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查看原文本刊更多论文

聚甘油硫酸盐和天然聚阴离子在2型炎症中的抗炎作用。

2型炎症是先天免疫系统和适应性免疫系统的重要防御机制，但当其失调时，可引起过敏性哮喘和特应性皮炎等慢性特应性疾病。胸腺基质淋巴生成素（TSLP）通过引导T细胞转向2型辅助细胞（TH2）亚型和刺激B细胞的抗体产生来帮助驱动2型炎症。纤维连接蛋白（FN）最近在儿童特应性皮炎的血浆中被发现水平升高，并在支气管上皮组织模型中显示出潜在的促炎作用。这两种蛋白质的表面电荷表明它们可能与带电分子相互作用。为了寻找对抗2型炎症的新策略，我们发现带负电荷的聚甘油硫酸盐与TSLP和FN强烈结合。我们证实这些分子通过减少tslp介导的CD4+ T细胞的2型极化来抑制炎症。我们发现，在fn触发的炎症支气管上皮模型中添加聚甘油硫酸酯可降低TSLP表达和白细胞介素6分泌。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.