Abstract
IL‐19 reduces TNF‐α‐driven mRNA abundance and protein abundance of intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) (p<0.01) in cultured coronary artery endothelial cells (ECs) as measured by RT‐PCR and immunoblot. IL‐19 treatment produced no change in activation of the transcription factor NF‐κB, as measured by immunoblot analysis of p65 phosphorylation, translocation, and IkB degradation. IL‐19 decreases stability of ICAM‐1 and VCAM‐1 mRNA in actinomycin‐D treated cells. IL‐19 treatment inhibits cytoplasmic translocation of the mRNA stability factor HuR as assayed by immunoblot and immunofluorescence. siRNA knock‐down of HuR also decreases ICAM‐1 and VCAM‐1 mRNA stability. IL‐19 decreases HuR cytoplasmic translocation and phosphorylation as measured by phospho‐serine immunoprecipitation of HuR. In cultured coronary artery smooth muscle cells (SMCs) and ECs, IL‐19 increases expression of putative HuR regulator microRNA‐133, measured using the miScript PCR system (Qiagen), and treatment with miR‐133 mimic reduced expression of HuR mRNA.These data support our hypothesis that IL‐19 exerts its anti‐inflammatory effects by HuR‐mediated decrease in mRNA stability. We propose inhibition of HuR phosphorylation and translocation and upregulation of miR‐133 as possible mechanisms.
Published Version
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