Repeated and alternate stimulations with dsRNA and SEB alter responses in macrophages and epithelial cells

IF 3.9 2区医学 Q2 ALLERGY

World Allergy Organization Journal Pub Date : 2025-02-01 DOI:10.1016/j.waojou.2025.101026

Jun-Pyo Choi, PhD , Yae-Eun Kim, BS , Min-Kyung Kim, MS , Mi-Hyun Kang, MS , Yu-Kyoung Hwang, MD , Jeong-Eun Yoon, MD , Yoon-Seok Chang, MD, PhD , Sae-Hoon Kim, MD, PhD

{"title":"Repeated and alternate stimulations with dsRNA and SEB alter responses in macrophages and epithelial cells","authors":"Jun-Pyo Choi, PhD , Yae-Eun Kim, BS , Min-Kyung Kim, MS , Mi-Hyun Kang, MS , Yu-Kyoung Hwang, MD , Jeong-Eun Yoon, MD , Yoon-Seok Chang, MD, PhD , Sae-Hoon Kim, MD, PhD","doi":"10.1016/j.waojou.2025.101026","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>The innate immune system is activated by foreign molecules via pattern recognition receptors and other surveillance systems, producing diverse cytokines that recruit and activate other immune cells. Recent studies have shown that once activated by foreign molecules, the innate immune system exhibits altered responses upon subsequent exposure to the same or different infectious agents, such as lipopolysaccharides (LPS) or bacteria. However, as these alterations in response to viral infection and staphylococcal enterotoxin B (SEB) in the airways have not been fully elucidated, we focused on the changes in immune responses induced by repeated stimulation of macrophages and epithelial cells with foreign molecules.</div></div><div><h3>Methods</h3><div>THP-1-derived macrophages and BEAS-2B epithelial cells were stimulated with dsRNA (double-stranded RNA) or SEB and cultured in fresh complete medium for 4 days. Subsequently, the cells were re-stimulated with different doses of dsRNA or SEB, and the cytokine and signal phosphorylation levels were evaluated.</div></div><div><h3>Results</h3><div>Repeated stimulation with high dose of dsRNA or SEB, induced an increase in IL-10, CCL2, CCL22, CCL24, CXCL10, and CXCL11 in macrophages, while only repeated stimulation with dsRNA stimulation resulted in an increase in IL-6, CCL2, CCL5, CCL24, CXCL11, and TGF-β in epithelial cells. Cross-stimulation with SEB-dsRNA induced an increase in CCL5, CCL20, CCL22, CCL24, CXCL10, and CXCL11 levels in macrophages. However, in epithelial cells, SEB-dsRNA stimulation increased the levels of CCL5, CXCL11, and TGF-β, while dsRNA-SEB stimulation elevated CCL1, CCL20, CXCL10, and CXCL11. These cytokine changes were driven by distinct phosphorylation patterns in macrophages and epithelial cells, depending on the type and intensity of stimuli.</div></div><div><h3>Conclusion</h3><div>Repeated stimulation with the same or cross-over stimuli induced alterations in the immune response of macrophages and epithelial cells. These observations indicated that persistent airway stimulation can lead to changes in airway inflammation, potentially leading to asthma.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 2","pages":"Article 101026"},"PeriodicalIF":3.9000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Allergy Organization Journal","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1939455125000018","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ALLERGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction

The innate immune system is activated by foreign molecules via pattern recognition receptors and other surveillance systems, producing diverse cytokines that recruit and activate other immune cells. Recent studies have shown that once activated by foreign molecules, the innate immune system exhibits altered responses upon subsequent exposure to the same or different infectious agents, such as lipopolysaccharides (LPS) or bacteria. However, as these alterations in response to viral infection and staphylococcal enterotoxin B (SEB) in the airways have not been fully elucidated, we focused on the changes in immune responses induced by repeated stimulation of macrophages and epithelial cells with foreign molecules.

Methods

THP-1-derived macrophages and BEAS-2B epithelial cells were stimulated with dsRNA (double-stranded RNA) or SEB and cultured in fresh complete medium for 4 days. Subsequently, the cells were re-stimulated with different doses of dsRNA or SEB, and the cytokine and signal phosphorylation levels were evaluated.

Results

Repeated stimulation with high dose of dsRNA or SEB, induced an increase in IL-10, CCL2, CCL22, CCL24, CXCL10, and CXCL11 in macrophages, while only repeated stimulation with dsRNA stimulation resulted in an increase in IL-6, CCL2, CCL5, CCL24, CXCL11, and TGF-β in epithelial cells. Cross-stimulation with SEB-dsRNA induced an increase in CCL5, CCL20, CCL22, CCL24, CXCL10, and CXCL11 levels in macrophages. However, in epithelial cells, SEB-dsRNA stimulation increased the levels of CCL5, CXCL11, and TGF-β, while dsRNA-SEB stimulation elevated CCL1, CCL20, CXCL10, and CXCL11. These cytokine changes were driven by distinct phosphorylation patterns in macrophages and epithelial cells, depending on the type and intensity of stimuli.

Conclusion

Repeated stimulation with the same or cross-over stimuli induced alterations in the immune response of macrophages and epithelial cells. These observations indicated that persistent airway stimulation can lead to changes in airway inflammation, potentially leading to asthma.

查看原文本刊更多论文

dsRNA和SEB的重复和交替刺激改变了巨噬细胞和上皮细胞的反应

先天免疫系统通过模式识别受体和其他监视系统被外来分子激活，产生各种细胞因子，招募和激活其他免疫细胞。最近的研究表明，一旦被外来分子激活，先天免疫系统在随后暴露于相同或不同的感染因子（如脂多糖（LPS）或细菌）时表现出改变的反应。然而，由于呼吸道对病毒感染和葡萄球菌肠毒素B （SEB）反应的这些改变尚未完全阐明，我们将重点放在了用外来分子反复刺激巨噬细胞和上皮细胞诱导的免疫反应的变化上。方法用双链RNA （dsRNA）或SEB刺激sthp -1来源的巨噬细胞和BEAS-2B上皮细胞，在新鲜完整培养基中培养4 d。随后，用不同剂量的dsRNA或SEB重新刺激细胞，并评估细胞因子和信号磷酸化水平。结果高剂量dsRNA或SEB重复刺激可诱导巨噬细胞IL-10、CCL2、CCL22、CCL24、CXCL10和CXCL11表达升高，而仅dsRNA重复刺激可导致上皮细胞IL-6、CCL2、CCL5、CCL24、CXCL11和TGF-β表达升高。SEB-dsRNA交叉刺激诱导巨噬细胞中CCL5、CCL20、CCL22、CCL24、CXCL10和CXCL11水平升高。然而，在上皮细胞中，SEB-dsRNA刺激增加了CCL5、CXCL11和TGF-β的水平，而dsRNA-SEB刺激升高了CCL1、CCL20、CXCL10和CXCL11的水平。这些细胞因子的变化是由巨噬细胞和上皮细胞中不同的磷酸化模式驱动的，这取决于刺激的类型和强度。结论相同或交叉刺激可引起巨噬细胞和上皮细胞免疫应答的改变。这些观察结果表明，持续的气道刺激可导致气道炎症的变化，从而可能导致哮喘。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

World Allergy Organization Journal Immunology and Microbiology-Immunology

CiteScore

9.10

自引率

5.90%

发文量

审稿时长

9 weeks

期刊介绍： The official pubication of the World Allergy Organization, the World Allergy Organization Journal (WAOjournal) publishes original mechanistic, translational, and clinical research on the topics of allergy, asthma, anaphylaxis, and clincial immunology, as well as reviews, guidelines, and position papers that contribute to the improvement of patient care. WAOjournal publishes research on the growth of allergy prevalence within the scope of single countries, country comparisons, and practical global issues and regulations, or threats to the allergy specialty. The Journal invites the submissions of all authors interested in publishing on current global problems in allergy, asthma, anaphylaxis, and immunology. Of particular interest are the immunological consequences of climate change and the subsequent systematic transformations in food habits and their consequences for the allergy/immunology discipline.