Abstract
BackgroundInterleukin (IL)-17 is an important factor in rheumatoid arthritis (RA) pathogenesis. MicroRNA (miRNA)s are a family of non coding RNAs and associated with human diseases including RA. The purpose of this study is to identify the miRNAs in the differentiation of IL-17 producing cells, and analyze their expression pattern in the peripheral blood mononuclear cells (PBMC) and synovium from RA patients.MethodsIL-17 producing cells were expanded from CD4+T cell. MiRNA microarray was performed to identify the miRNAs in the differentiation of IL-17 producing cells. Quantitative polymerase chain reaction was performed to examine the expression patterns of the identified miRNAs in the PBMC and synovium from RA and osteoarthritis (OA) patients. Double staining combining in situ hybridization and immunohistochemistry of IL-17 was performed to analyze the expression pattern of identified miRNA in the synovium.ResultsSix miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells. The expression of miR-146a and IL-17 was higher than in PBMC in the patients with low score of Larsen grade and short disease duration. MiR-146a intensely expressed in RA synovium in comparison to OA. MiR-146a expressed intensely in the synovium with hyperplasia and high expression of IL-17 from the patients with high disease activity. Double staining revealed that miR-146a expressed in IL-17 expressing cells.ConclusionThese results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients. There is the possibility that miR-146a participates in the IL-17 expression.
Highlights
Interleukin (IL)-17 is an important factor in rheumatoid arthritis (RA) pathogenesis
Several microRNAs exhibit a tissue-specific or developmental stage-specific expression pattern and have been reported to be associated with human diseases such as cancer, leukemia, and viral infection [22,23]. These findings suggest their potential as a novel therapeutic target. miRNA might play a role in RA pathogenesis in autoimmune and other chronic inflammatory diseases including of RA
These findings suggest that miRNA might play a role in the expression of IL-17, and an analysis of the expression pattern of miRNAs in IL-17 producing T cells might lead to the development of new treatments for RA
Summary
Interleukin (IL)-17 is an important factor in rheumatoid arthritis (RA) pathogenesis. Several microRNAs exhibit a tissue-specific or developmental stage-specific expression pattern and have been reported to be associated with human diseases such as cancer, leukemia, and viral infection [22,23]. These findings suggest their potential as a novel therapeutic target. Changsheng Du et al reported that miR-326 regulates Th-17 differentiation and associated with the pathogenesis of multiple sclerosis[27] These findings suggest that miRNA might play a role in the expression of IL-17, and an analysis of the expression pattern of miRNAs in IL-17 producing T cells might lead to the development of new treatments for RA
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