原发性干燥综合征患者唇腺中 Bcl-2、Fas 和 FasL 水平与炎症程度的关系。

Association between Increased Bcl-2, Fas and FasL Levels and Inflammation Extent in Labial Salivary Glands During Primary Sjögren's Syndrome.

机构信息

Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Group, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria.

Department of Biology and Cellular Physiology, Faculty of Biological Sciences, Saad Dahlab\'s University of Blida, Blida, Algeria.

出版信息

Endocr Metab Immune Disord Drug Targets. 2022;22(3):328-338. doi: 10.2174/1871530321666210809155147.

DOI:10.2174/1871530321666210809155147

PMID:34370657

Abstract

BACKGROUND

Primary Sjögren Syndrome (pSS) is a chronic autoimmune disease characterized by epithelial atrophy, mononuclear infiltration in exocrine glands resulting in the defective function of these glands. In pSS, atrophy of the epithelium is caused by an increased amount of apoptosis.

OBJECTIVE

The main aim of this study is to investigate the role of the apoptosis-related factors by studying Bcl-2, Fas and FasL expression in relation to the extent of inflammation as well as the effect of therapy on the expression of these mediators.

METHODS

In pSS patients (n=62) documented for their serological and clinical features, Fas, FasL and Bcl-2 plasma levels were assessed using enzyme-linked immunosorbent assays. In the same context, we investigated their expression by immunohistochemistry analysis in the labial salivary glands samples in association with the extent of inflammation.

RESULTS

Interestingly, our results indicated that in pSS patients, the plasmatic Bcl-2, Fas and FasL levels, which appeared to be associated with the severity of inflammation and were significantly elevated in comparison to the healthy controls. Moreover, a significant decrease in all these factors was observed in patients after combined corticosteroids-hydroxychloroquine therapy. Importantly, we report a strong positive correlation between Bcl-2 and NO levels. The immunohistochemical staining reveals a strong Bcl-2 expression in infiltrating mononuclear cells and a total absence in the acinar cells. The Bcl-2 level varies according to the severity of pathology. However, the expression of Fas and FasL was less important and predominantly localized in infiltrating mononuclear cells.

CONCLUSION

Our current study highlights the involvement of Bcl-2, Fas and FasL in pSS glands injury. These factors may act as useful predictor markers of a clinical course in pSS, suggesting a novel approach in the pSS patients monitoring.

摘要

背景

原发性干燥综合征（pSS）是一种慢性自身免疫性疾病，其特征为上皮萎缩、单核细胞浸润外分泌腺，导致这些腺体功能缺陷。在 pSS 中，上皮萎缩是由凋亡增加引起的。

目的

本研究的主要目的是通过研究 Bcl-2、Fas 和 FasL 的表达与炎症程度的关系，以及治疗对这些介质表达的影响，来探讨凋亡相关因素的作用。

方法

在 pSS 患者（n=62）的血清学和临床特征记录中，使用酶联免疫吸附试验评估 Fas、FasL 和 Bcl-2 的血浆水平。在同一背景下，我们通过免疫组织化学分析研究了它们在唇腺样本中的表达，以及与炎症程度的关系。

结果

有趣的是，我们的结果表明，在 pSS 患者中，Bcl-2、Fas 和 FasL 的血浆水平似乎与炎症的严重程度有关，与健康对照组相比显著升高。此外，在接受联合皮质激素-羟氯喹治疗后，所有这些因素均显著降低。重要的是，我们报告了 Bcl-2 和 NO 水平之间存在强烈的正相关。免疫组织化学染色显示浸润性单核细胞中有强烈的 Bcl-2 表达，而在腺泡细胞中则完全不存在。Bcl-2 水平根据病理严重程度而变化。然而，Fas 和 FasL 的表达则不那么重要，主要定位于浸润性单核细胞中。