Dataset Information

Perturbation of transcriptome in non-neoplastic salivary gland epithelial cell lines derived from patients with primary Sjogren's syndrome.

ABSTRACT: The data presented here are related to the research article titled "Impaired anti-inflammatory activity of PPAR? in the salivary epithelia of Sjögren's syndrome patients imposed by intrinsic NF-?B activation" (Vakrakou et al., Journal of Autoimmunity, in press, 2017). In the cited manuscript, using comparative analyses of salivary gland biopsy specimens and ductal salivary gland epithelial cell (SGEC) lines from SS patients and disease controls, we have demonstrated that the ductal epithelia of SS patients display constitutively reduced PPAR? expression, transcriptional activity and anti-inflammatory function that were associated with cell-autonomously activated NF-?B and IL-1? pathways in these cells. Herein, the comparative transcriptome analysis of SGEC lines is presented. We show that the ductal epithelia of SS patients with severe lymphoepithelial lesions manifest constitutive perturbation in various inflammation- and metabolism related signaling pathways.

SUBMITTER: Vakrakou AG

PROVIDER: S-EPMC5988450 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Perturbation of transcriptome in non-neoplastic salivary gland epithelial cell lines derived from patients with primary Sjögren's syndrome.

Vakrakou Aigli G AG Polyzos Alexandros A Kapsogeorgou Efstathia K EK Thanos Dimitris D Manoussakis Menelaos N MN

Data in brief 20171212

The data presented here are related to the research article titled <i>"Impaired anti-inflammatory activity of PPARγ in the salivary epithelia of Sjögren's syndrome patients imposed by intrinsic NF-κB activation</i>" (Vakrakou et al., Journal of Autoimmunity, in press, 2017). In the cited manuscript, using comparative analyses of salivary gland biopsy specimens and ductal salivary gland epithelial cell (SGEC) lines from SS patients and disease controls, we have demonstrated that the ductal epithe ...[more]

PMID: 29876386

Similar Datasets

Project description:ObjectiveA major characteristic of the autoimmune disease primary Sjögren's syndrome (SS) is salivary gland (SG) hypofunction. The inability of resident SG stem cells (SGSCs) to maintain homeostasis and saliva production has never been explained and limits our comprehension of mechanisms underlying primary SS. The present study was undertaken to investigate the role of salivary gland stem cells in hyposalivation in primary SS.MethodsSGSCs were isolated from parotid biopsy samples from controls and patients classified as having primary SS or incomplete primary SS, according to the American College of Rheumatology/European League Against Rheumatism criteria. Self-renewal and differentiation assays were used to determine SGSC regenerative potential, RNA was extracted for sequencing analysis, single telomere length analysis was conducted to determine telomere length, and frozen tissue samples were used for immunohistochemical analysis.ResultsSGSCs isolated from primary SS parotid gland biopsy samples were regeneratively inferior to healthy control specimens. We demonstrated that SGSCs from samples from patients with primary SS are not only lower in number and less able to differentiate, but are likely to be senescent, as revealed by telomere length analysis, RNA sequencing, and immunostaining. We further found that SGSCs exposed to primary SS-associated proinflammatory cytokines we induced to proliferate, express senescence-associated genes, and subsequently differentiate into intercalated duct cells. We also localized p16+ senescent cells to the intercalated ducts in primary SS SG tissue, suggesting a block in SGSC differentiation into acinar cells.ConclusionThis study represents the first characterization of SGSCs in primary SS, and also the first demonstration of a linkage between an autoimmune disease and a parenchymal premature-aging phenotype. The knowledge garnered in this study indicates that disease-modifying antirheumatic drugs used to treat primary SS are not likely to restore saliva production, and should be supplemented with fresh SGSCs to recover saliva production.

Project description:Primary Sjögren’s syndrome (SS or autoimmune epithelitis) is a relatively common autoimmune disorder that is primarily characterized by chronic lymphoepithelial inflammatory reactions in the exocrine glands, mainly the salivary and lachrymal glands. It may extend from disease confined to the exocrine glands (organ-specific exocrinopathy) to various extraglandular manifestations (systemic disease) and the development of B-cell lymphoma. Several studies from our laboratory had provided evidence for the strong implication of ductal salivary gland epithelial cells (SGEC) in the pathogenesis of Sjögren’s syndrome (SS), including the development of salivary gland infiltrating lesions and of adverse systemic clinical complications, such as the development of B-cell lymphoma. In fact, the comparative assessment of non-neoplastic SGEC lines derived from SS patients and disease controls had indicated that the ductal epithelia of SS patients manifest an “intrinsically activated” status that is associated with distinct aberrant phenotypic and functional features encountered in “inflamed” cells. Herein, using microarray analysis, we sought to comparatively analyze the constitutive gene expression in long-term cultured non-neoplastic SGEC lines derived from non-SS sicca control individuals and from SS patients. The study aimed to reveal the genes that are differentially expressed between SGEC lines derived from SS patients and controls, as well as between SGEC lines derived from SS patients with moderate lymphocytic infiltrations (focus score<2; SS-Group-1) and SS patients with severe lymphocytic infiltrations (focus score ≥2; SS-Group-2). The transcriptome profiling analysis presented herein lends further support to the intrinsic activation status of patients’ ductal epithelia and its association with distinct proinflammatory and metabolism-related gene signatures, which occur primarily among patients with heavy tissue infiltrates and high risk for lymphoma development.

Project description:Objective: Salivary gland ultrasound (SGUS) is emerging as a valid tool in the management of primary Sjögren's syndrome (pSS). This study aimed to investigate whether pSS patients with normal-appearing or pathological SGUS findings showed different clinical, laboratory, and pathologic pSS-related features, and to compare the results by using two different SGUS scores. Methods: Consecutive pSS patients, according to the ACR-EULAR classification criteria, were evaluated. Salivary glands were scored using the early 1992 score by De Vita et al. and the latest 2019 OMERACT score, both being semiquantitative 0-3 scoring systems focused on ultrasonographic parenchymal inhomogeneity (grades 0 and 1, normal-appearing; grades 2 and 3, pathological). The patients were then divided into two groups: "SGUS normal-appearing" if all the salivary glands had normal-appearing parenchyma (grade 0 or 1), or "SGUS pathological" if the grade was 2 or 3 in at least one salivary gland. The associations between SGUS and pSS-related clinical, laboratory, and pathological features were then investigated in the two groups. Results: One hundred pSS patients were evaluated, the mean age (±SD) was 60.9 ± 12.0 years, and mean disease duration was 11.7 ± 7.2 years. Twenty-nine out of 100 (29%) patients were in the "SGUS normal-appearing" group and 71/100 (71%) were in the "SGUS pathological" group. A normal-appearing SGUS was significantly associated with the absence of anti-La/SSB antibodies (p < 0.001) and normal unstimulated salivary flow rate (p = 0.02) by both univariate and multivariate analyses. By univariate analysis, a normal-appearing SGUS was significantly associated also with the absence of rheumatoid factor (p = 0.002) and of serum monoclonal component (p = 0.003), ESSDAI < 5 (p = 0.03), and with a negative lip biopsy (p = 0.029). No associations were found with other items, including anti-Ro/SSA (p = 0.145), Schirmer's test (p = 0.793), ESSPRI (p = 0.47), and demographic data. No differences in these results were observed by using the two SGUS scoring systems. Conclusion: The SGUS allowed the identification of different phenotypes of pSS, and different SGUS scores focused on salivary gland inhomogeneity may be effective to this end.

Dataset Information

Perturbation of transcriptome in non-neoplastic salivary gland epithelial cell lines derived from patients with primary Sjogren's syndrome.

Publications

Perturbation of transcriptome in non-neoplastic salivary gland epithelial cell lines derived from patients with primary Sjögren's syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets