| First Author | Guo G | Year | 2020 |
| Journal | Mol Immunol | Volume | 128 |
| Pages | 219-226 | PubMed ID | 33157351 |
| Mgi Jnum | J:326819 | Mgi Id | MGI:6791503 |
| Doi | 10.1016/j.molimm.2020.10.023 | Citation | Guo G, et al. (2020) Gfi1 and Zc3h12c orchestrate a negative feedback loop that inhibits NF-kB activation during inflammation in macrophages. Mol Immunol 128:219-226 |
| abstractText | NF-kappaB activation is essential in mediating the induction of pro-inflammatory cytokines and also plays a key role in regulating the inflammatory response through intricate mechanisms. In this study, loss of Gfi1 was found to be associated with transcriptomic profiles related to NF-kappaB activation, including an increase in pro-inflammatory cytokines. Genetically inactivating the IKK/NF-kappaB signaling pathway in macrophages showed that Gfi1 deficiency led to pro-inflammatory cytokine production requiring NF-kappaB activation. More importantly, we revealed that one of the under-researched mechanisms, involving Gfi1 and Zc3h12c exerted negative regulation on NF-kappaB activation. Both Gfi1 and Zc3h12c were found to inhibit NF-kappaB activation, and double knockout exhibited additive roles of Gfi1 and Zc3h12c in preventing proinflammatory cytokine production. The loss of Gfi1 upregulated Zc3h12c which in turn inhibited NF-kappaB activation. Therefore, this study delineates the function of Zc3h12c in enhancing the negative regulation of Gfi1 through NF-kappaB activation during inflammation in macrophages. |
