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TLR4 的全身上调导致变应性鼻炎中脂多糖诱导的鼻细胞因子释放增加。

Systemic up-regulation of TLR4 causes lipopolysaccharide-induced augmentation of nasal cytokine release in allergic rhinitis.

机构信息

Division of ENT Diseases, CLINTEC, Karolinska University Hospital, Stockholm, Sweden.

出版信息

Int Arch Allergy Immunol. 2012;159(1):6-14. doi: 10.1159/000335196. Epub 2012 Apr 27.

DOI:10.1159/000335196
PMID:22555057
Abstract

BACKGROUND

Allergic rhinitis is a systemic disorder, and it is clinically well recognized that it can be aggravated by infection. Activation of the innate immune system constitutes a critical element in the process. Toll-like receptors (TLRs) comprise a part of the innate immune system, and lipopolysaccharide (LPS)-induced activation of TLR4 represents bacterial-induced interactions in various model systems. The present study examines how TLR2 and TLR4 expression is affected by symptomatic allergic rhinitis, and if LPS added upon allergen affects nasal cytokine release.

METHODS

In patients with pollen-induced allergic rhinitis and healthy non-allergic volunteers, nasal lavage (NAL), peripheral blood and bone marrow were sampled before and during the pollen season. TLR2 and TLR4 expression was determined flow cytometrically. Changes in the TLR receptor expression pattern were evaluated by a nasal challenge with allergen followed by LPS, or vice versa. Symptoms along with cells and cytokines in NAL were analyzed.

RESULTS

TLR4 expression increased in leukocytes in NAL, peripheral blood and bone marrow during symptomatic allergic rhinitis. A similar increase was seen for TLR2 in neutrophils in blood. Nasal challenge with allergen followed by LPS augmented the release of IL-4, IL-5, IL-10, IL-13, IFN-γ and TNF-α.

CONCLUSION

A systemic up-regulation of TLR4 in symptomatic allergic rhinitis may explain why LPS preceded by allergen increases nasal cytokine release.

摘要

背景

过敏性鼻炎是一种全身性疾病,临床上公认其可因感染而加重。固有免疫系统的激活是这一过程的关键因素。Toll 样受体(TLRs)构成固有免疫系统的一部分,脂多糖(LPS)诱导的 TLR4 激活代表了各种模型系统中细菌诱导的相互作用。本研究探讨了症状性过敏性鼻炎如何影响 TLR2 和 TLR4 的表达,以及过敏原中添加 LPS 是否会影响鼻细胞因子的释放。

方法

在花粉诱导的过敏性鼻炎患者和健康非过敏性志愿者中,在花粉季节之前和期间采集鼻灌洗液(NAL)、外周血和骨髓。采用流式细胞术测定 TLR2 和 TLR4 的表达。通过过敏原加 LPS 的鼻挑战或反之,评估 TLR 受体表达模式的变化。分析 NAL 中的症状以及细胞和细胞因子。

结果

在有症状的过敏性鼻炎期间,NAL、外周血和骨髓中的白细胞中 TLR4 表达增加。血液中的中性粒细胞中 TLR2 的表达也增加。过敏原加 LPS 的鼻挑战增加了 IL-4、IL-5、IL-10、IL-13、IFN-γ 和 TNF-α 的释放。

结论

在有症状的过敏性鼻炎中 TLR4 的全身性上调可能解释了为什么过敏原前的 LPS 会增加鼻细胞因子的释放。

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