https://scholars.lib.ntu.edu.tw/handle/123456789/542178
標題: | Aberrant expression of microRNAs in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis | 作者: | Lai N.-S. Yu H.-C. Chen H.-C. CHIA-LI YU Huang H.-B. Lu M.-C. |
關鍵字: | Ankylosing spondylitis; Interferon gamma; Let-7i; MicroRNA; T cells; Toll-like receptor-4 | 公開日期: | 2013 | 卷: | 173 | 期: | 1 | 起(迄)頁: | 47-57 | 來源出版物: | Clinical and Experimental Immunology | 摘要: | Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by dysregulated T cells. We hypothesized that the aberrant expression of microRNAs (miRNAs) in AS T cells involved in the pathogenesis of AS. The expression profile of 270 miRNAs in T cells from five AS patients and five healthy controls were analysed by real-time polymerase chain reaction (PCR). Thirteen miRNAs were found potentially differential expression. After validation, we confirmed that miR-16, miR-221 and let-7i were over-expressed in AS T cells and the expression of miR-221 and let-7i were correlated positively with the Bath Ankylosing Spondylitis Radiology Index (BASRI) of lumbar spine in AS patients. The protein molecules regulated by miR-16, miR-221 and let-7i were measured by Western blotting. We found that the protein levels of Toll-like receptor-4 (TLR-4), a target of let-7i, in T cells from AS patients were decreased. In addition, the mRNA expression of interferon (IFN)-γ was elevated in AS T cells. Lipopolysaccharide (LPS), a TLR-4 agonist, inhibited IFN-γ secretion by anti-CD3+anti-CD28 antibodies-stimulated normal T cells but not AS T cells. In the transfection studies, we found the increased expression of let-7i enhanced IFN-γ production by anti-CD3+anti-CD28+ lipopolysaccharide (LPS)-stimulated normal T cells. In contrast, the decreased expression of let-7i suppressed IFN-γ production by anti-CD3+anti-CD28+ LPS-stimulated AS T cells. In conclusion, we found that miR-16, miR-221 and let-7i were over-expressed in AS T cells, but only miR-221 and let-7i were associated with BASRI of lumbar spine. In the functional studies, the increased let-7i expression facilitated the T helper type 1 (IFN-γ) immune response in T cells. 2013 British Society for Immunology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84878810703&doi=10.1111%2fcei.12089&partnerID=40&md5=5aacca174a6fee444213c25f93afea14 https://scholars.lib.ntu.edu.tw/handle/123456789/542178 |
ISSN: | 0009-9104 | DOI: | 10.1111/cei.12089 | SDG/關鍵字: | C reactive protein; CD28 antigen; CD3 antibody; gamma interferon; HLA B27 antigen; interstitial collagenase; microRNA; microRNA 16; microRNA 221; protein; protein let 7i; toll like receptor 4; unclassified drug; adult; ankylosing spondylitis; article; clinical article; controlled study; disease activity; female; genetic transfection; human; immunopathogenesis; interferon production; leukemia cell line; lumbar spine; male; priority journal; protein degradation; protein expression; sacroiliitis; T lymphocyte; Adult; Arthritis, Rheumatoid; Case-Control Studies; Cells, Cultured; Female; Gene Expression Regulation; Humans; Interferon-gamma; Jurkat Cells; Lipopolysaccharides; Lumbar Vertebrae; Lupus Erythematosus, Systemic; Male; MicroRNAs; Middle Aged; RNA, Messenger; Severity of Illness Index; Spondylitis, Ankylosing; Th1 Cells; Toll-Like Receptor 4; Young Adult |
顯示於: | 醫學系 |
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