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

Abstract

Background: Primary Sjögren syndrome (pSS) is a chronic autoimmune disease characterized by epithelial atrophy, mononuclear infiltration in exocrine glands resulting in 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 appear 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 the 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.

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“…Indeed, apoptosis of SGECs is considered an essential pathogenetic mechanism for SS development through the accumulation of apoptotic debris and autoantigen discharge, which can activate the immune response [15,40]. In accord with these findings, it has been recently reported that increased plasma levels of pro-apoptotic molecules, including Bcl2, Fas, and FasL, are associated with more severe inflammation status in SS patients than controls [41]. Moreover, overexpression of lysosome-associated membrane glycoprotein 3 (LAMP3)-a lysosomal protein playing a central role in antigen presentation and cell survival-in SS-derived MSGs has been associated with increased SGEC apoptosis and higher serum autoantibodies in SS patients [42].…”

Network pharmacology and molecular docking analysis on the mechanism of Tripterygium wilfordii Hook in the treatment of Sjögren syndrome

“…In patients with SS, plasma BCL2 is associated with the severity of inflammation, and significantly increased compared with healthy controls. [ 30 ]…”

Exploring the relationship between oxidative stress status and inflammatory markers during primary Sjögren’s syndrome: A new approach for patient monitoring

“…Despite the fact that NO is considered as a key signaling molecule in several physiological activities, however, like most other inflammatory mediators, excessive production of NO in response to inflammatory stimuli mediate cellular/tissue injury. 24 – 27 Importantly, NO is a crucial marker for oxidative stress and inflammation. 28 Our report revealed a high rise in NO levels, which can result in the production of peroxynitrite.…”