Increased microRNA-146a/b, TRAF6 gene and decreased IRAK1 gene expressions in the peripheral mononuclear cells of patients with Sjögren's syndrome

2012 ◽  
Vol 141 (2) ◽  
pp. 165-168 ◽  
Author(s):  
Erika Zilahi ◽  
Tünde Tarr ◽  
Gábor Papp ◽  
Zoltán Griger ◽  
Sándor Sipka ◽  
...  
2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Weiqian Chen ◽  
Jin Lin ◽  
Heng Cao ◽  
Danyi Xu ◽  
Bei Xu ◽  
...  

The activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjögren’s syndrome (pSS). The inhibitor ofκB (IκB) kinase (IKK) family such as IKKα, IKKβ, IKKγ, and IKKε, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/εin patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKε(pIKKε), pIκBα, and pNF-κB p65 (p-p65) were highly expressed in ductal epithelium and infiltrating mononuclear cells by immunohistochemistry, compared to healthy individuals. pIKKα/βand pIKKγwere both negative. And pIKKεpositively related to expression of p-p65. Furthermore, pIKKεand p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKKε, total IKKε, pIKKα/β, and p-p65 were significantly increased by western blot, compared to healthy controls. However, there was no difference in IKKγand IκBαbetween pSS patients and healthy individuals. These results demonstrated an abnormality of IKKε, IκBα, and NF-κB in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKKεexpression and deregulation of NF-κB pathway.


2020 ◽  
Vol 9 (10) ◽  
pp. 3299
Author(s):  
Katarzyna Błochowiak ◽  
Piotr Celichowski ◽  
Bartosz Kempisty ◽  
Katarzyna Iwanik ◽  
Michał Nowicki

Sjögren’s syndrome (SS) is characterized by xerostomia. We aimed to investigate and compare gene expressions in the labial salivary glands of SS patients with xerostomia SS (sicca) and without xerostomia SS (non-sicca) and of healthy subjects (HS) by means of microarray analysis, and to find genes involved in xerostomia. The study group comprised 11 SS patients (3 SS (sicca) and 8 SS (non-sicca)) and 9 HS. The relative gene expression changes were validated with RT-qPCR in the larger study group. Among the differently expressed genes belonging to the “secretion” ontology group with a fold change >2 and with a p value < 0.05, the Transmembrane P24 Trafficking Protein 10 (TMED10), Protein Disulfide Isomerase Family A Member 4 (PDIA4), Calnexin (CANX), Amyloid Beta Precursor Protein (APP), and Transmembrane BAX Inhibitor Motif Containing 6 (TMBIM6) gene expressions in both SS (sicca) and SS (non-sicca) groups were lower than in HS. Significant correlations were observed between TMED10, PDIA4, and CANX gene expression in SS (sicca) patients compared to the controls. There were no differences between the SS (sicca) and SS (non-sicca) study groups in the expression of the aforementioned genes. Results indicate their role in the endoplasmic reticulum system, their overlapping function and the loss of the APP neuroprotective function in xerostomia. It has a multifactorial origin and can be triggered by disturbances to the various signaling pathways in saliva secretion.


1983 ◽  
Vol 14 (4) ◽  
pp. 455-461 ◽  
Author(s):  
Suzanne M. de la Monte ◽  
Grover M. Hutchins ◽  
Prabodh K. Gupta

2019 ◽  
Vol 8 (9) ◽  
pp. 1349 ◽  
Author(s):  
Dolcino ◽  
Tinazzi ◽  
Vitali ◽  
Papa ◽  
Puccetti ◽  
...  

Primary Sjögren’s syndrome (pSjS) is a chronic systemic autoimmune disorder, primarily affecting exocrine glands; its pathogenesis is still unclear. Long non-coding RNAs (lncRNAs) are thought to play a role in the pathogenesis of autoimmune diseases and a comprehensive analysis of lncRNAs expression in pSjS is still lacking. To this aim, the expression of more than 540,000 human transcripts, including those ascribed to more than 50,000 lncRNAs is profiled at the same time, in a cohort of 16 peripheral blood mononuclear cells PBMCs samples (eight pSjS and eight healthy subjects). A complex network analysis is carried out on the global set of molecular interactions among modulated genes and lncRNAs, leading to the identification of reliable lncRNA-miRNA-gene functional interactions. Taking this approach, a few lncRNAs are identified as targeting highly connected genes in the pSjS transcriptome, since they have a major impact on gene modulation in the disease. Such genes are involved in biological processes and molecular pathways crucial in the pathogenesis of pSjS, including immune response, B cell development and function, inflammation, apoptosis, type I and gamma interferon, epithelial cell adhesion and polarization. The identification of deregulated lncRNAs that modulate genes involved in the typical features of the disease provides insight in disease pathogenesis and opens avenues for the design of novel therapeutic strategies.


2009 ◽  
Vol 36 (5) ◽  
pp. 989-996 ◽  
Author(s):  
WEI-SHENG CHEN ◽  
KUAN-CHIA LIN ◽  
CHUN-HSIUNG CHEN ◽  
HSIEN-TZUNG LIAO ◽  
HON-PIN WANG ◽  
...  

Objective.Sjögren’s syndrome (SS) is an inflammatory autoimmune disease. We investigated important factors associated with the expression of inflammation-related molecules in minor salivary gland (MSG) mononuclear cells in patients with SS.Methods.Thirty-four patients with SS with a MSG biopsy grading of either grade III (10 patients) or grade IV (24 patients) were enrolled. The age, sex, autoantibodies, cell infiltration, and intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), or CXCR3 expression were also analyzed.Results.Ten of the 34 patients with SS were diagnosed with secondary SS; in these patients, the diagnosis of rheumatoid arthritis was confirmed in 8 and systemic lupus erythematosus in 2. TRAIL and ICAM-1 were overexpressed in patients with antinuclear antibodies (ANA) > 1:160, compared to those with titer < 1:160 (45.1 ± 4.4 vs 41.2 ± 3.9, p = 0.021, and 15.2 ± 5.7 vs 10.8 ± 3.3, p = 0.018, respectively). Higher erythrocyte sedimentation rate (ESR; ≥ 20) was associated with higher TRAIL expression and CD20 cell infiltration in contrast to lower ESR (< 20; p < 0.05). ICAM-1, TRAIL, and MMP-3 were expressed more predominantly in anti-SSA-positive than in anti-SSA-negative patients with SS. There was a significant difference in CD20 cell infiltration and MMP-3 expression between primary SS and secondary SS. Biopsy of a grade IV showed a significantly increased expression of TRAIL (44.9 ± 4.5 vs 40.8 ± 3.6, p = 0.013) and MMP-3 (62.7 ± 6.3 vs 54.4 ± 7.3, p = 0.003) in mononuclear cells as compared to those of grade III.Conclusion.In our study, pathologic grading with a higher grade (grade IV) and the presence of SSA or a higher titer of ANA were significantly associated with the overexpression of TRAIL, MMP-3, or ICAM-1 in the salivary gland mononuclear cells in patients with SS.


VASA ◽  
2008 ◽  
Vol 37 (Supplement 73) ◽  
pp. 26-32 ◽  
Author(s):  
Schlattmann ◽  
Höhne ◽  
Plümper ◽  
Heidrich

Background: In order to analyze the prevalence of Raynaud’s syndrome in diseases such as scleroderma and Sjögren’s syndrom – a meta-analysis of published data was performed. Methods: The PubMed data base of the National Library of Medicine was used for studies dealing with Raynaud’s syndrome and scleroderma or Raynaud’s syndroem and Sjögren’s syndrom respectively. The studies found provided data sufficient to estimate the prevalence of Raynaud’s syndrome. The statistical analysis was based on methods for a fixed effects meta-analysis and finite mixture model for proportions. Results: For scleroderma a pooled prevalence of 80.9% and 95% CI (0.78, 0.83) was obtained. A mixture model analysis found four latent classes. We identified a class with a very low prevalence of 11%, weighted with 0.15. On the other hand there is a class with a very high prevalence of 96%. Analysing the association with Sjögren’s syndrome, the pooled analysis leads to a prevalence of Raynaud’s syndrome of 32%, 95% CI(26.7%, 37.7%). A mixture model finds a solution with two latent classes. Here, 38% of the studies show a prevalence of 18.8% whereas 62% observe a prevalence of 38.3%. Conclusion: There is strong variability of studies reporting the prevalence of Raynaud’s syndrome in patients suffering from scleroderma or Sjögren’s syndrome. The available data are insufficient to perform a proper quantitative analysis of the association of Raynaud’s phenomenon with scleroderma or Sjögren’s syndrome. Properly planned and reported epidemiological studies are needed in order to perform a thorough quantitative analysis of risk factors for Raynaud’s syndrome.


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