POM121 inhibits the macrophage inflammatory response by impacting NF-κB P65 nuclear accumulation

Experimental Cell Research
Wenlong GeSidong Xiong

Abstract

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-α 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 POM121fl/fl Lyzm-Cre+ mice compared to those in control mice, as evidenced by the more severe lung injury and inflammation, increased TNF-α 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-κB 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 compo...Continue Reading

Citations

Dec 21, 2019·Expert Review of Molecular Diagnostics·Tengqi WangLizhou Jia
Dec 10, 2020·Genetic Testing and Molecular Biomarkers·Shidong ZhangShengkui Tan
Dec 17, 2020·Development·Valeria GuglielmiMaximiliano A D'Angelo
Jun 8, 2021·The Journal of Biological Chemistry·Qingtang ShenAlexander F Palazzo

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