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哮喘患者外周血单个核细胞上 Toll 样受体的表达;对哮喘管理的影响。

Toll-like receptor expression on peripheral blood mononuclear cells in asthmatics; implications for asthma management.

机构信息

Department of Internal Medicine, Seoul National University, 28 Yongondong, Chongno-gu, Seoul, 110-744, Republic of Korea.

出版信息

J Clin Immunol. 2010 May;30(3):459-64. doi: 10.1007/s10875-009-9363-z. Epub 2010 Jan 14.

Abstract

BACKGROUND

Accumulating evidence indicates that cells expressing Toll-like receptors (TLRs) play an important role in allergic diseases. The authors undertook this study to explore the hypothesis that TLR-mediated inflammatory signals are important from the perspective of asthma management.

METHODS

The expressions of TLR1, TLR2, TLR3, TLR4, TLR6, and TLR9 and levels of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8, and IFN-gamma) on the peripheral blood mononuclear cells (PBMCs) of 36 stable asthmatics on treatment (the on-treatment group), 15 asthmatics (the treatment-naïve group) before and after a 7-day course of oral prednisolone (30 mg/day), and on the PBMCs of 15 healthy controls were measured after in vitro stimulation using TLR-specific ligands.

RESULTS

In the on-treatment group, TLR1, TLR2, TLR6, and TLR9 expressions on PBMCs were significantly different between asthmatics and controls. And the expression of TLR4 on PBMCs and TNF-alpha production stimulated by lipopolysaccharide (LPS), were significantly higher in mild to moderate than in severe asthmatics. Interestingly, in the treatment-naïve group, short-term prednisolone significantly increased LPS-induced TNF-alpha and IFN-gamma productions by PBMCs.

CONCLUSION

TLR-mediated inflammatory signals contribute to the development and severity of asthma and are not reduced by glucocorticoid treatment, which suggests that a TLR-specific antagonist and glucocorticoid are required for the effective control of airway inflammation in asthmatics.

摘要

背景

越来越多的证据表明表达 Toll 样受体 (TLR) 的细胞在过敏性疾病中发挥重要作用。作者开展这项研究旨在从哮喘管理的角度探索 TLR 介导的炎症信号很重要的假说。

方法

作者检测了 36 名经治疗的稳定期哮喘患者(治疗组)、15 名治疗前哮喘患者(治疗前组)和 15 名健康对照者外周血单个核细胞(PBMC)中 TLR1、TLR2、TLR3、TLR4、TLR6 和 TLR9 的表达以及促炎细胞因子(TNF-α、IL-1β、IL-6、IL-8 和 IFN-γ)水平,这些患者均接受了为期 7 天的口服泼尼松龙(30mg/天)治疗,并用 TLR 特异性配体进行体外刺激。

结果

治疗组中,哮喘患者与健康对照者的 PBMC 中 TLR1、TLR2、TLR6 和 TLR9 的表达存在显著差异。而且,中重度哮喘患者的 PBMC 中 TLR4 表达和脂多糖(LPS)刺激产生的 TNF-α明显高于轻度哮喘患者。有趣的是,治疗前组中,短期泼尼松龙治疗明显增加了 LPS 诱导的 PBMC 产生 TNF-α和 IFN-γ。

结论

TLR 介导的炎症信号有助于哮喘的发生和严重程度,糖皮质激素治疗不能降低这些信号,这表明哮喘患者气道炎症的有效控制需要 TLR 特异性拮抗剂和糖皮质激素联合治疗。

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