| First Author | Alam Z | Year | 2020 |
| Journal | Cell Rep | Volume | 31 |
| Issue | 13 | Pages | 107825 |
| PubMed ID | 32610126 | Mgi Jnum | J:303319 |
| Mgi Id | MGI:6514459 | Doi | 10.1016/j.celrep.2020.107825 |
| Citation | Alam Z, et al. (2020) Counter Regulation of Spic by NF-kappaB and STAT Signaling Controls Inflammation and Iron Metabolism in Macrophages. Cell Rep 31(13):107825 |
| abstractText | Activated macrophages must carefully calibrate their inflammatory responses to balance efficient pathogen control with inflammation-mediated tissue damage, but the molecular underpinnings of this "balancing act" remain unclear. Using genetically engineered mouse models and primary macrophage cultures, we show that Toll-like receptor (TLR) signaling induces the expression of the transcription factor Spic selectively in patrolling monocytes and tissue macrophages by a nuclear factor kappaB (NF-kappaB)-dependent mechanism. Functionally, Spic downregulates pro-inflammatory cytokines and promotes iron efflux by regulating ferroportin expression in activated macrophages. Notably, interferon-gamma blocks Spic expression in a STAT1-dependent manner. High levels of interferon-gamma are indicative of ongoing infection, and in its absence, activated macrophages appear to engage a "default" Spic-dependent anti-inflammatory pathway. We also provide evidence for the engagement of this pathway in sterile inflammation. Taken together, our findings uncover a pathway wherein counter-regulation of Spic by NF-kappaB and STATs attune inflammatory responses and iron metabolism in macrophages. |
