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Department of Immunobiology and Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06520-8089
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.
Address correspondence and reprint requests to Jordan S. Pober, Yale University School of Medicine, Amistad Research Building, 10 Amistad Street, New Haven, CT 06520 or Yajaira Suárez at the current address: Department of Medicine, Leon H. Charney Division of Cardiology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, Smilow 8, 522 First Avenue, New York, NY 10016. E-mail addresses: Jordan.pober{at}yale.edu or yajaira.suarez{at}nyumc.org
1 Current address: Department of Medicine, Leon H. Charney Division of Cardiology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY 10016.
This work was supported by National Institutes of Health Grants R01-HL36003 and HL51014 (to J.S.P.) and a Scientist Development Grant from the American Heart Association (0835481N) (to Y.S.). C.W. was supported by a National Institutes of Health Medical Scientist Training Program (T32-GM07205STP).
The sequences presented in this article have been submitted to MIAMExpress under accession number E-MTAB-150.
The online version of this article contains supplemental material.
Abbreviations used in this paper:
CI, control inhibitor sequence; CM, control mimic sequence; EC, endothelial cell; HDF, human dermal fibroblast; miRNA, microRNA; QRT-PCR, quantitative real-time PCR; SELE, E-selectin; UTR, untranslated region; VE-cadherin, vascular endothelial cadherin; VEGF, vascular endothelial growth factor.
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