further showed that ectopic miR-146a caused a reduction of both basal and IL-1b stimulated expression of COX-2 protein. Conversely, an upregulation of the COX-2 protein was observed after knockdown of miR-146a with LNA-anti-miR-146a in IL-1b - treated cells. The anti-inflammatory role of miR-146a is also supported by its ability to regulate the IL-1b induced release of several other proinflammatory factors, such as IL-6, IL-8, G-CSF, IFN-c, IP-10, MIP-1b, and TNF-a, HMGB1 and MCP1. Although IL-1ß increased miR-146a levels, these levels were not sufficient to significantly reduce the expression of the miR-146a targets studied. However, we cannot exclude a physiological control on the levels that could be reached in the absence of miR- 146a production. Accordingly, transfection with LNA in the presence of IL-1ß which blocked the effect of miR-146a, further increased IRAK-1 and IRAK-2 mRNA, as well as IL-6 and COX-2 mRNA and protein levels in vitro. 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