Inducible MicroRNA-132 Inhibits the Production of Inflammatory Cytokines by Targeting TRAF6, TAK1, and TAB1 in Teleost Fish.

Abstract

The innate immune response is the first line of defense against pathogen infection. Eradication of pathogen infection requires appropriate immune and inflammatory responses, but excessive inflammation may cause inflammatory and autoimmune diseases. MicroRNAs (miRNAs) are a group of small noncoding RNAs, and accumulating evidence has shown that in mammals, they can act as negative regulators that participate in the regulation of inflammation and immune responses. However, the miRNA-mediated immune regulation networks in the inflammatory responses of lower vertebrates are largely unknown. In this study, we report an miRNA, miR-132, identified from miiuy croaker, that acts as a negative regulator in the host's bacterium-induced inflammatory response. We found that miR-132 expression was dramatically increased upon infection by the Gram-negative bacterium Vibrio harveyi and lipopolysaccharide (LPS). Inducible miR-132 inhibits the production of inflammatory cytokines by targeting tumor necrosis factor receptor-associated factor 6 (TRAF6), transforming growth factor-activated protein kinase 1 (TAK1), and TAK1 binding protein 1 (TAB1), thus avoiding an excessive inflammatory response. Furthermore, we demonstrate that miR-132 modulates the inflammatory response through a TRAF6-, TAK1-, and TAB1-mediated NF-κB signaling pathway. These results collectively reveal that miR-132 plays a negative regulatory role in the host antibacterial immune response, which will help to gain insight into the intricate network of host resistance to pathogen infection in lower vertebrates.