Altered let-7 expression in Myasthenia gravis and let-7c mediated regulation of IL-10 by directly targeting IL-10 in Jurkat cells

Int Immunopharmacol. 2012 Oct;14(2):217-23. doi: 10.1016/j.intimp.2012.07.003. Epub 2012 Jul 24.

Abstract

Myasthenia gravis (MG) is a T cell-dependent and B cell-mediated autoimmune disease of neuromuscular junctions and cytokines may play a crucial role in the pathogenesis and perpetuation of MG. MicroRNAs (miRNAs) have been implicated as fine-tuning regulators controlling diverse biological processes at the level of posttranscriptional repression. Dysregulation of miRNAs has been described in various disease states. In this study, miRNA microarrays identified let-7 family to be decreased in peripheral blood mononuclear cells (PBMCs) from MG patients compared to the healthy controls. We next demonstrated the differential expression of let-7 family in larger samples by quantitative real-time PCR. Using a combination of bioinformatics and molecular approaches, we confirmed IL-10 as a target for let-7c. IL-10 expression also showed a negative correlation with let-7c expression in PBMCs from MG patients. Further experiments revealed that induced levels of IL-10 were inversely related to let-7c levels. We also showed that let-7c could regulate IL-10 expression in Jurkat cells. In summary, our results suggest that abnormal expression/regulation of microRNAs may contribute to or be indicative of the initiation and progression of MG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Gene Expression Regulation / immunology
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Jurkat Cells
  • Leukocytes, Mononuclear / immunology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microarray Analysis
  • Myasthenia Gravis / genetics
  • Myasthenia Gravis / immunology*

Substances

  • MicroRNAs
  • mirnlet7 microRNA, human
  • Interleukin-10