Intraindividual variation of microRNA expression levels in plasma and peripheral blood mononuclear cells and the associations of these levels with the pathogenesis of autoimmune thyroid diseases.

BACKGROUND: microRNAs (miRNAs) circulate in the blood and negatively regulate the expression of mRNAs. Some miRNAs are associated with the development of autoimmune thyroid diseases (AITD); however, there are few reports on the association between miRNA expression and the pathogenesis of AITD or the physiological variations of circulating miRNAs, which are important to examine as biomarkers. METHODS: We examined the circadian and day-to-day variations in the expression levels of 5 miRNAs (miR-125a, miR-146a, miR-155, let-7e and miR-106a) in plasma and peripheral blood mononuclear cells (PBMC). We also analysed the expression levels of two of these miRNAs (miR-146a and miR-155) in 20 healthy controls, 60 Graves' disease (GD) patients and 50 Hashimoto's disease (HD) patients. RESULTS: For each miRNA, we observed wide intraindividual variation [coefficient of variation value (CV): 70%-100%] compared to measurement error (CV: 20%-40%). In patients with AITD, HD, GD in remission and mild HD, the expression levels of miR-146a in PBMC were increased 296%, 328%, 348% and 464% above the levels in healthy controls, respectively (p=0.0443 and p=0.0273, p=0.0267 and p=0.0052, respectively). In severe HD, the expression level of miR-155 in plasma was increased to 347% of that in healthy controls (p=0.0256). CONCLUSIONS: The expression levels of miRNAs in plasma and PBMC showed wide intraindividual variation. In addition, miR-146a may be associated with the development of AITD.

Increases of microRNA let-7e in peripheral blood mononuclear cells in Hashimoto's disease.

MicroRNA (miRNA) is a family of non-coding RNAs that have important roles in various vital functions. It has been reported that let-7e, a miRNA, may be involved in the regulation of interleukin (IL)-10 production. The purpose of this study was to evaluate the role of let-7e as a regulator of IL-10 production in the pathological processes of autoimmune thyroid diseases (AITDs). We evaluated the association between let-7e expression and intracellular expression of IL-10 in the peripheral blood mononuclear cells (PBMCs) collected from 11 healthy volunteers. Then we investigated the expression levels of let-7e in the PBMCs of 50 patients with Graves' disease (GD), 42 patients with Hashimoto's disease (HD) and 28 healthy controls. We found negative correlations between the expression level of let-7e and IL-10 messengerRNA (mRNA) and between the expression level of let-7e and proportion of IL-10(+) cells in stimulated PBMCs from healthy volunteers (r = -0.44, p = 0.0267 and r = -0.49, p = 0.0166, respectively). The expression levels of let-7e were significantly increased in HD patients compared with those in GD patients and healthy volunteers (p = 0.0003 and p = 0.0011, respectively). let-7e may be associated with the pathogenesis of HD through the regulation of intracellular IL-10 expression.

Specific induction of oxidative stress in terminal bronchiolar Clara cells during dimethylarsenic-induced lung tumor promoting process in mice.

The induction of oxidative stress in pulmonary cells during the process of lung tumor promotion by dimethylarsinic acid (DMA), a main metabolite of inorganic arsenics in mammals, was examined by immunohistochemical analysis using a specific antibody against 4-hydroxy-2-nonenal (4HNE) adducts, which are major aldehydic metabolites of lipid peroxidation. We demonstrated that 4HNE-modified proteins existed specifically in the secretory granules in terminal bronchiolar Clara cells. Furthermore, the degree of positive staining increased with the duration of DMA administration. Transmission electron microscopy revealed morphological changes in the Clara cells of DMA-treated mice. These results suggest that Clara cells are the major target cell for DMA-induced oxidative stress and that the cells may play an important role in the lung tumor promotion process in mice.