The inducible microRNA-203 in fish represses the inflammatory responses to Gram-negative bacteria by targeting IL-1 receptor-associated kinase 4 [Gene Regulation]

December 14th, 2017 by Tianjun Xu, Qing Chu, Junxia Cui, Xueyan Zhao

Innate immune responses are the first defense against pathogenic invaders. Activation and termination of these immune responses are regulated by several mechanisms. MicroRNAs (miRNAs), a group of small non-coding RNAs, have been implicated in the regulation of a spectrum of both physiological and pathological conditions, including immune responses. Although immune regulatory miRNAs networks in higher vertebrates have been well described, regulation of these responses in fish species is poorly understood in fish species. In the present study, we investigated the role of the miRNA miR-203 involved in inflammatory responses in miiuy croaker (Miichthys miiuy). We found that the Gram-negative bacterium, Vibrio anguillarum and LPS significantly upregulated host miR-203 expression. The increased miR-203 expression suppressed the production of inflammatory cytokines and thereby prevented mounting of a full immune response. Mechanistically, we identified and validated IL-1 receptor-associated kinase 4 (IRAK4) as a target of miR-203. We observed that miR-203 could post-transcriptionally controls IRAK4 expression and thereby inhibits the activation of nuclear factor kappa B (NF-κB) signaling. In summary, our findings reveal that miR-203 in fish is a critical suppressor of innate immune responses to bacterial infection by suppressing a feedback to IRAK4-NF-κB-mediated signaling in fish.
  • Posted in Journal of Biological Chemistry, Publications
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