Abo Al Hayja Muntasir, Eklund Anders, Grunewald Johan, Wahlström Jan
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.
J Inflamm (Lond). 2015 Apr 9;12:28. doi: 10.1186/s12950-015-0071-6. eCollection 2015.
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.
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.
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.
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.
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。
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。
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。
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。
