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Altered micro‐ RNA 21 expression correlates with enhanced peripheral IL ‐23p19 levels patients with primary Sjögren's syndrome
Author(s) -
Ni Gabhann J.,
Pilson Q.,
Jefferies C.,
Murphy C.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0532
Subject(s) - pathogenesis , inflammation , peripheral blood mononuclear cell , cytokine , microrna , interleukin 6 , gene expression , immunology , medicine , tumor necrosis factor alpha , systemic inflammation , endocrinology , gene , biology , in vitro , biochemistry
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 pSS patients. 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, mi RNA ‐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, SOCS 1 – potent anti‐inflammatory regulators) and miR‐21 ( IL 12p35 and PDCD 4, 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.