The Inducible microRNA-21 Negatively Modulates the Inflammatory Response in Teleost Fish via Targeting IRAK4

Qing Chu,Lihua Liu,Tianjun Xu,Xiaolong Yan

doi:10.3389/fimmu.2019.01623

Abstract

Eradication of bacterial infection requires timely and appropriate immune and inflammatory responses, but excessive induction of inflammatory cytokines can cause acute or chronic inflammatory disorders. Thus, various layers of negative regulators and mechanisms are needed to ensure maintenance of the homeostasis for the immune system. miRNAs are a family of small non-coding RNAs that emerged as significant and versatile regulators involved in regulation of immune responses. Recently, the molecular mechanisms of miRNA in host-pathogen interaction networks have been extensively studied in mammals, whereas the underlying regulatory mechanisms in fish are still poorly understood. In this study, we identify miR-21 as a negative regulator of the teleost inflammatory response. We found that lipopolysaccharide and Vibrio anguillarum significantly upregulated the expression of fish miR-21. Upregulated miR-21 suppresses LPS-induced inflammatory cytokine expression by targeting IL-1 receptor-associated kinase 4 (IRAK4), thereby avoiding excessive inflammatory responses. Furthermore, we demonstrated that miR-21 regulates inflammatory responses through NF-κB signaling pathways. The collective findings indicate that miR-21 plays a regulatory role in host-pathogen interactions through IRAK4-mediated NF-κB signaling pathway.

Highlights

MicroRNAs are highly conserved, single-stranded, small non-coding RNAs that have been shown to act as essential regulators of gene expression at the posttranscriptional level. miRNAs induce gene degradation and suppression of translation, or both, mainly by imperfect binding to miRNA recognition elements (MREs) within the 3′-untranslated region (UTR) of target mRNAs [1]
E; Supplementary Figure 1, the expression of miR21 was highly expressed in liver and spleen samples, and reached its peak at 72 h and 48 h after infections, respectively. These data indicated that miR-21 expression can be increased by LPS and V. anguillarum and that miR-21 may participate in the regulation of immune responses upon Gram-negative bacterial infection
We demonstrated that miR-21 acts as negative effectors involved in the regulation of fish inflammatory response upon Gram-negative bacterial infections

Summary

Introduction

MicroRNAs (miRNAs) are highly conserved, single-stranded, small non-coding RNAs that have been shown to act as essential regulators of gene expression at the posttranscriptional level. miRNAs induce gene degradation and suppression of translation, or both, mainly by imperfect binding to miRNA recognition elements (MREs) within the 3′-untranslated region (UTR) of target mRNAs [1]. Many miRNAs have been reported to regulate diverse biological processes, such as embryogenesis, tumorigenesis, differentiation, immunity, and inflammation [3, 4]. Innate immune and inflammatory responses are normal self-protection mechanism that eliminate pathogens and resist microbial invaders [5, 6]. TLRs participate in controlling multiple aspects of the innate immune response. Following recognition of TLR ligands, TLRs elicit innate immunity by activating multiple intracellular signaling cascades including variable adaptor proteins and transcriptional factors. Activation of NF-κB result in the transcription of various inflammatory genes, including TNF-α and IL-6, to sense microbial pathogens [7,8,9]. To maintain a balance between host preservation and inflammatory pathology, the immune response and inflammation need to be tightly regulated

Methods

Results

Conclusion