Cutting edge: TNF-induced microRNAs regulate TNF-induced expression of E-selectin and intercellular adhesion molecule-1 on human endothelial cells: feedback control of inflammation.
MicroRNAs (miRNAs) pair with target sequences in the 3' untranslated region of mRNAs to posttranscriptionally repress gene expression. In this study, we report that TNF-mediated induction of endothelial adhesion molecules can be regulated by miRNAs that are induced by TNF. Specifically, E-selectin and ICAM-1 are targets of TNF-induced miRNAs miR-31 and miR-17-3p, respectively. Specific antagonism of these TNF-induced miRNAs increased neutrophil adhesion to cultured endothelial cells. Conversely, transfections with mimics of these miRNAs decreased neutrophil adhesion to endothelial cells. These data suggest that miRNAs provide negative feedback control of inflammation.
Suárez
Yajaira
Y
Department of Immunobiology and Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06520-8089, USA. yajaira.suarez@nyumc.org
Wang
Chen
C
Manes
Thomas D
TD
Pober
Jordan S
JS
D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis* / Q000235:genetics; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D025461:Feedback, Physiological / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D019040:E-Selectin; C524941:MIRN17 microRNA, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1