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非 Löfgren 型结节病患者支气管肺泡灌洗(BAL)液和血液 T 细胞中过氧化物酶体增殖物激活受体α表达降低。

Reduced expression of peroxisome proliferator-activated receptor alpha in BAL and blood T cells of non-löfgren's sarcoidosis patients.

作者信息

Abo Al Hayja Muntasir, Eklund Anders, Grunewald Johan, Wahlström Jan

机构信息

Department of Medicine and CMM, Respiratory Medicine Unit, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden ; Lung Research Laboratory L4:01, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden.

Department of Medicine and CMM, Respiratory Medicine Unit, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.

出版信息

J Inflamm (Lond). 2015 Apr 9;12:28. doi: 10.1186/s12950-015-0071-6. eCollection 2015.

Abstract

BACKGROUND

Sarcoidosis is a granulomatous disease affecting in particular the lungs. The peroxisome proliferator-activated receptors (PPARs) play important regulatory roles in inflammation. The aim of this study was to gain more insight about the expression of all three PPARs (α, β/δ and γ) in sarcoidosis.

METHODS

Bronchoalveolar lavage (BAL) cells and peripheral blood cells were obtained from healthy controls (HC) and sarcoidosis patients with Löfgren's syndrome (LS) and without Löfgren's syndrome (non-LS). PPARs mRNA expression was analyzed in total BAL cells and in FACS (Fluorescence-activated cell sorting) sorted alveolar macrophages (AM) and CD4(+) T cells respectively by comparative RT-PCR. PPARs protein expression was analyzed in AM, and in BAL and blood CD4(+) and CD8(+) T cells by flow cytometry.

RESULTS

In BAL CD4(+) T cells, we noticed a significantly lower PPARα mRNA expression in sarcoidosis patients compared with HC. In non-LS patients, a significantly lower PPARα protein expression in BAL CD4(+) T cells was detected as compared with LS patients. In peripheral blood CD4(+) T cells, non-LS patients had a significantly lower expression of PPARα and PPARγ compared with LS patients.

CONCLUSION

The lower protein expression of PPARα and PPARγ could contribute to the persistent T-cell driven inflammation noted especially in non-resolving sarcoidosis, common in non-LS patients.

摘要

背景

结节病是一种主要影响肺部的肉芽肿性疾病。过氧化物酶体增殖物激活受体(PPARs)在炎症中发挥重要调节作用。本研究的目的是更深入了解结节病中所有三种PPARs(α、β/δ和γ)的表达情况。

方法

从健康对照(HC)以及患有 Löfgren 综合征(LS)和未患有 Löfgren 综合征(非 LS)的结节病患者中获取支气管肺泡灌洗(BAL)细胞和外周血细胞。分别通过比较逆转录聚合酶链反应(RT-PCR)分析总 BAL 细胞以及经荧光激活细胞分选(FACS)分选的肺泡巨噬细胞(AM)和 CD4(+) T 细胞中 PPARs mRNA 的表达。通过流式细胞术分析 AM、BAL 和血液中 CD4(+)和 CD8(+) T 细胞中 PPARs 蛋白的表达。

结果

在 BAL CD4(+) T 细胞中,我们注意到结节病患者的 PPARα mRNA 表达明显低于 HC。在非 LS 患者中,与 LS 患者相比,检测到 BAL CD4(+) T 细胞中 PPARα 蛋白表达明显降低。在外周血 CD4(+) T 细胞中,与 LS 患者相比,非 LS 患者的 PPARα 和 PPARγ 表达明显降低。

结论

PPARα 和 PPARγ 较低的蛋白表达可能导致特别是在非缓解性结节病(常见于非 LS 患者)中持续存在的 T 细胞驱动的炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/4428503/35b4e15e7cf8/12950_2015_71_Fig1_HTML.jpg

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