MicroRNA-93 inhibits inflammatory cytokine production in LPS-stimulated murine macrophages by targeting IRAK4

•miR-93 is downregulated in the eyes of LPS-induced EIU rats.•miR-93 is downregulated in LPS-treated RAW 264.7 cells.•miR-93 inhibits LPS-induced inflammatory cytokine production.•miR-93 inhibits LPS-induced activation of NF-κB signaling through IRAK4. Endotoxin-induced uveitis (EIU) is an animal mo...

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Veröffentlicht in:FEBS letters 2014-05, Vol.588 (9), p.1692-1698
Hauptverfasser: Xu, Yan, Jin, Huiyi, Yang, Xiaolu, Wang, Lili, Su, Li, liu, Kun, Gu, Qing, Xu, Xun
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Sprache:eng
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Zusammenfassung:•miR-93 is downregulated in the eyes of LPS-induced EIU rats.•miR-93 is downregulated in LPS-treated RAW 264.7 cells.•miR-93 inhibits LPS-induced inflammatory cytokine production.•miR-93 inhibits LPS-induced activation of NF-κB signaling through IRAK4. Endotoxin-induced uveitis (EIU) is an animal model of acute ocular inflammation for the study of human endogenous anterior uveitis. The mechanisms accounting for the development of ocular inflammation remain hazy. MicroRNAs (mi-RNAs) have been proposed as novel regulators of inflammation. It remains unclear whether a microRNA-mediated regulatory mechanism is involved in LPS-induced EIU. In this study, we report that miR-93 expression in the eyes of EIU rats and LPS-stimulated macrophages is significantly decreased. We also show that miR-93 inhibits NF-κB activation and pro-inflammatory cytokines by targeting IRAK4 expression. We further demonstrate that miR-93 inhibits IRAK4 expression by binding directly to the 3′-UTR of IRAK4. Our findings suggest that miR-93 is a negative regulator of the immune response in EIU.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2014.03.013