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Lipopolysaccharide Exposure Alleviates Asthma in Mice by Regulating Th1/Th2 and Treg/Th17 Balance.
Medical Science Monitor Pub Date : 2018-05-17 , DOI: 10.12659/msm.905202
Fengxia Ding 1 , Zhou Fu 1 , Bo Liu 2
Affiliation  

BACKGROUND It is generally believed that endotoxin exposure exacerbates risk of developing asthmatic symptoms. However, recent studies have indicated that prior bacterial exposure may prevent future symptoms of asthma. Here, we evaluated the influence of pre-exposure to different concentrations of lipopolysaccharide (LPS) to subsequent ovalbumin (OVA) allergen sensitization and challenge. MATERIAL AND METHODS Four-week-old Balb/c mice were treated intranasally with varying concentrations of LPS (1 ug, 10 ug, and 100 ug) or sterile PBS for 10 days, then 2 weeks later they were exposed to OVA. Both the molecular and functional airway responses to OVA administration were assessed following prior exposure to different doses of LPS or controls. Additionally, the Th1/Th2 and Treg/Th17 balance was measured. RESULTS Airway responsiveness and immune cell recruitment in the bronchoalveolar lavage (BALF) were decreased in animals exposed to a low dose of LPS (1 ug) treatment compared with the asthma group. Moderate-dose (10 ug) and high-dose (100 ug) LPS administration showed no differences from controls. Further, low-dose LPS (1 ug) exposure was associated with increased Th1 cytokines, T-bet, Treg cytokine (IL-10, TGF-β), and Foxp3 expression, but decreased Th2 cytokines (IL-4,5,13), GATA3, Th17, and ROR-gt expression compared with the asthma group. Finally, higher numbers of CD4+CD25+Foxp3+Treg cells, and CD4+INF-γ+T cells, and lower CD4+IL-4+T cells and CD4+IL-17+T cells were observed in the low-dose LPS-treated groups compared to controls. CONCLUSIONS Our findings suggest that prior exposure to low doses of LPS may protect from OVA-induced airway hyperresponsiveness (AHR) and histopathologic changes through regulation of the Th1/Th2 and Treg/Th17 balance.

中文翻译:

脂多糖暴露通过调节Th1 / Th2和Treg / Th17平衡来减轻小鼠哮喘。

背景技术通常认为内毒素暴露会加剧发生哮喘症状的风险。但是,最近的研究表明,事先接触细菌可能会预防将来的哮喘症状。在这里,我们评估了预先暴露于不同浓度的脂多糖(LPS)对随后的卵清蛋白(OVA)过敏原致敏和激发的影响。材料与方法用不同浓度的LPS(1 ug,10 ug和100 ug)或无菌PBS鼻内处理四周大的Balb / c小鼠10天,然后2周后将它们暴露于OVA。在事先接触不同剂量的LPS或对照后,评估了对OVA给药的分子和功能性气道反应。另外,测量了Th1 / Th2和Treg / Th17平衡。结果与哮喘组相比,接受低剂量LPS​​(1 ug)治疗的动物气道反应性和支气管肺泡灌洗(BALF)中的免疫细胞募集减少。中剂量(10 ug)和大剂量(100 ug)LPS给药与对照组无差异。此外,低剂量LPS​​(1 ug)暴露与Th1细胞因子,T-bet,Treg细胞因子(IL-10,TGF-β)和Foxp3表达增加有关,但Th2细胞因子减少(IL-4、5、13 ),GATA3,Th17和ROR-gt表达与哮喘组相比。最后,在低剂量时观察到较高数量的CD4 + CD25 + Foxp3 + Treg细胞和CD4 +INF-γ+ T细胞,而较低CD4 + IL-4 + T细胞和CD4 + IL-17 + T细胞与对照组相比,LPS治疗组。
更新日期:2019-11-01
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