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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

Yale University, New Haven, Connecticut, United States
The Journal of Immunology (Impact Factor: 5.36). 11/2009; 184(1):21-5. DOI: 10.4049/jimmunol.0902369
Source: PubMed

ABSTRACT 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.

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    • "In mice, but not humans, P-selectin transcription is induced as well (Pan et al. 1998). TNF also induces miRs that feedback and limit E-selectin and ICAM-1 expression (Suarez et al. 2010). TNF and IL-1 also induce synthesis of chemokines, notably of IL-8 and MCP-1, the principal human chemokines that activate neutrophils and monocytes, respectively. "
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