| First Author | Ge W | Year | 2019 |
| Journal | Exp Cell Res | Volume | 377 |
| Issue | 1-2 | Pages | 17-23 |
| PubMed ID | 30802453 | Mgi Jnum | J:274793 |
| Mgi Id | MGI:6295788 | Doi | 10.1016/j.yexcr.2019.02.021 |
| Citation | Ge W, et al. (2019) POM121 inhibits the macrophage inflammatory response by impacting NF-kappaB P65 nuclear accumulation. Exp Cell Res 377(1-2):17-23 |
| abstractText | The nuclear pore membrane protein 121 (POM121) was originally thought to be a constitutive protein of the nuclear pore complex (NPC). In addition to being involved in NPC assembly, abnormal POM121 expression has been found to be associated with many diseases. In this study, we explored, in detail, the effect of POM121 on the macrophage inflammatory response and found that its expression was significantly lower in LPS-stimulated macrophages, substantially amplifying pro-inflammatory cytokine (TNF-alpha and IL-6) production, suggesting that POM121 exerts a potent inhibitory effect on macrophage inflammation. Consistent with this notion, greater susceptibility to LPS-induced acute lung injury (ALI) as well as more severe tissue inflammation were found in POM121(fl/fl) Lyzm-Cre+mice compared to those in control mice, as evidenced by the more severe lung injury and inflammation, increased TNF-alpha and IL-6 production and more abundant proteins in bronchoalveolar lavage fluid (BALF). This inflammation-modulating effect of POM121 relied on its ability to repress the NF-kappaB signal pathway via inhibition of phosphorylated P65 (phos-P65) nuclear accumulation. In the present study, we reported that in addition to acting as a constitutive NPC component, POM121 also modulated LPS-induced macrophage inflammation via repressing nuclear P65 translocation. Our study may pave the way for regulating LPS-induced massive macrophage inflammation and providing evidence for the functional diversity of nucleoporins (Nups). |
