A Newly Identified MicroRNA, mmu-miR-7578, Functions as a Negative Regulator on Inflammatory Cytokines Tumor Necrosis Factor-α and Interleukin-6 via Targeting Egr1 in Vivo

Appropriate innate immune responses are required to protect an organism against foreign pathogens, and the immune response must be tightly controlled. Here, we report a new microRNA (miRNA) identified from a small RNA library from the epididymis, termed miR-7578, that acts as a negative regulator of inflammatory responses. It was abundantly expressed in immune-related organs and induced by lipopolysaccharide in the lung and epididymis, as well as macrophages stimulated with diverse Toll-like receptor ligands, in an NF-kappa B-dependent manner. mmu-miR-7578 inhibited the release of pro-inflammatory cytokines, including TNF alpha and IL6, by regulating its target gene Egr1, which encodes a transcription factor that activates TNF alpha and NF-kappa B expression. Transgenic mice overexpressing mmu-miR-7578 displayed higher resistance to endotoxin shock and lower plasma levels of TNF alpha and IL6, indicating that this miRNA acted as a negative molecule of immune response. In sum, we report a previously uncharacterized LPS-responsive miRNA that controls inflammatory response in a feedback loop by fine-tuning a key transcription factor in vivo.