However, we still demonstrated that the IFN-γ

mRNA expression levels were increased in AS T cells. Therefore, we propose that the increased let-7i expression in AS T cells activate the Th1 immune responses upon LPS stimulation. Although we showed that increased let-7i expression in T cells could suppress TLR-4 expression, it is premature to conclude that decreased TLR-4 expression on AS T cells contributed directly to this phenomenon. Instead, PD-1 inhibiton other molecule(s) involving the T cell signalling pathway targeted by let-7i might play an essential role. Selbach et al. demonstrated [49] that one miRNA can translationally repress hundreds of target genes. Nevertheless, the downstream molecular mechanism of increased let-7i expression stimulating a T helper type 1 (Th1)

(IFN-γ) immune response requires more detailed studies. O’Hara et al. [50] demonstrated that let-7i expression was suppressed by nuclear factor-kappa B (NF-κB), and many medications used for AS treatment have the potential to suppress NF-κB activity [51]. However, AS is a chronic inflammatory disease; the elevation of NF-κB DNA binding activity in lymphocytes could persist even after several months of adequate therapy [52]. In addition, we observed two newly diagnosed AS patients in this study who had not yet been treated with immunosuppressant. Their T cell let-7i expression levels appeared to be no different from those of the treated AS patients. Therefore, we consider that the increased expression of let-7i was irrelevant to treatment Selleck VX809 with immunosuppressive drugs. Therefore, the increased let-7i expression is a direct effect from AS disease per se and is involved in AS pathogenesis. In contrast, the expression of Bcl-2 targeted by miR-16 remained unchanged in AS T cells compared with normal T cells (Fig. 3b). This is because other molecules and signalling pathways may compensate Bcl-2 expression that was suppressed by miR-16. In http://www.selleck.co.jp/products/azd9291.html T cell lineage, the expression of

c-kit target by miR-221 is limited to the progenitor T cells, and lost gradually upon differentiation [53]. Thus the expression of c-kit could not be detected in T cells from peripheral blood in our study (Fig. 4b). In addition to AS T cells, over-expression of miR-16 was also found in peripheral mononuclear cells from RA patients [16] and activated normal T cells [54]. It is possible that the increased expression of miR-16 and miR-221 in AS patients may trigger inflammatory reactions. The inter-relationships among these three miRNAs and their respective target molecules require further investigation. Recently, the expression of miRNAs was under the control of epigenetic mechanisms such as DNA methylation.