Altered micro-RNA21 expression correlates with enhanced peripheral IL-23p19 levels patients with primary Sjögren's syndrome
Abstract
Purpose
Sjögren's syndrome (SS) is a systemic autoimmune disorder characterized by inflammation that affects mucous membranes particularly those of the exocrine glands, causing dry eyes and dry mouth. Previous investigations have suggested that dysregulated systemic inflammation contributes to the development and pathogenesis of SS. This study aimed to investigate potential mechanisms responsible for over production of pathogenic cytokines in SS patients.
Methods
Peripheral blood mononuclear cells and serum were prepared from whole blood taken from both healthy controls and pSSpatients. Gene induction and micro-RNA expression were analysed by real-time PCR. Cytokine levels were determined by ELISA.
Results
We observed significantly enhanced expression of the pro-inflammatory micro-RNA, miR-155 (p ≤ 0.05) and significantly reduced levels of the IL-10 promoting miR, miRNA-21 (p ≤ 0.05) compared to healthy controls. In keeping with this altered pattern of miR expression we observed significantly increased serum levels of pro-inflammatory cytokines (IL-6, IL-8 and TNF-a) as well as the Th17 promoting cytokine, IL-23p19 (p ≤ 0.05). Altered expression of previously identified targets of miR-155 (SHIP-1, SOCS1 – potent anti-inflammatory regulators) and miR-21 (IL12p35 and PDCD4, positive regulators of inflammation) was also observed. Significantly a moderate negative correlation (r = −0.657, p ≤ 0.05) was observed between reduced miR-21 expression and increased peripheral IL-23p19 levels in pSS patients, suggesting a link between altered miR expression and disease pathogenesis.
Conclusions
Our data suggest that abnormal expression or regulation of miRs and consequently miR regulated genes in innate immunity may contribute to the initiation and progression of SS via overproduction of pathogenic cytokines.
