| First Author | Zhang J | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 6 | Pages | 4310-20 |
| PubMed ID | 23184950 | Mgi Jnum | J:195583 |
| Mgi Id | MGI:5484830 | Doi | 10.1074/jbc.M112.351197 |
| Citation | Zhang J, et al. (2013) A newly identified microRNA, mmu-miR-7578, functions as a negative regulator on inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 via targeting Egr1 in vivo. J Biol Chem 288(6):4310-20 |
| abstractText | 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-kappaB-dependent manner. mmu-miR-7578 inhibited the release of pro-inflammatory cytokines, including TNFalpha and IL6, by regulating its target gene Egr1, which encodes a transcription factor that activates TNFalpha and NF-kappaB expression. Transgenic mice overexpressing mmu-miR-7578 displayed higher resistance to endotoxin shock and lower plasma levels of TNFalpha 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. |
