Pharmacological effects of β-D-mannuronic acid (M2000) on miR-146a,IRAK1,TRAF6 and NF-κB gene expression,as target molecules in inflammatory reactions

Background impaired expression and function of micrornas (mirnas) are involved in the pathogenesis of many autoimmune and inflammatory diseases. moreover,there is a close relationship between tlrs and mirnas and impairment in regulating their expression which can play a vital role in the immunopathogenesis of many inflammatory reactions. this research aimed to study the pharmaceutical effects of m2000 (β-d-mannuronic acid) on the expression of mir-146a and its two target molecules (irak1 and traf6),and the transcription factor nf-κb in the hek-blue htlr2 cell line. methods the cytotoxicity of m2000 was assessed by the mtt assay,and the qrt-pcr technique was employed in the presence and absence of m2000 treatment to measure gene-expression levels of mir-146a,irak1,traf6,and nf-κb. results mtt assay indicated that m2000 (before the concentration of 500 μg/ml) had no cytotoxic effect on hek-blue htlr2 cells. our results showed that m2000 at low and high doses (5 and 25 μg/well) could significantly reduce gene expression levels of mir-146a (p < 0.01). furthermore,it was found that this medication at two different doses could considerably decrease irak1 and traf6 gene expression (p < 0.001). moreover,this study revealed that expression level of nf-κb also significantly declined at these two doses (p < 0.01). conclusions this study for the first time shows that m2000 as a novel nsaid with immunosuppressive properties is able to modify tlr signaling through suppressing the adaptor molecules irak1 and traf6,the transcription factor nf-κb and mir-146a as a new therapeutic approach. © 2017 institute of pharmacology,polish academy of sciences