The Nuclear Factor-kappa B (NF-κB) pathway is vital for immune system regulation and pro-inflammatory signaling. Many inflammatory disorders and diseases, including cancer, are linked to dysregulation of NF-κB signaling. When macrophages recognize the presence of a pathogen, the signaling pathway is activated, resulting in the nuclear translocation of the transcription factor, NF-κB, to turn on pro-inflammatory genes. Here, we demonstrate the effects of a novel microtubule depolymerizer, NT-07-16, a polysubstituted pyrrole compound, on this process. Treatment with NT-07-16 decreased the production of pro-inflammatory cytokines in RAW264.7 mouse macrophages. It appears that the reduction in pro-inflammatory mediators produced by the macrophages after exposure to NT-07-16 may be due to activities upstream of the translocation of NF-κB into the nucleus. NF-κB translocation occurs after its inhibitory protein, IκB-α is phosphorylated which signals for its degradation releasing NF-κB so it is free to move into the nucleus. Previous studies from other laboratories indicate that these processes are associated with the microtubule network. Our results show that exposure to the microtubule-depolymerizer, NT-07-16 reduces the phosphorylation of IκB-α and also decreases the association of NF-κB with tubulin which may affect the ability of NF-κB to translocate into the nucleus. Therefore, the anti-inflammatory activity of NT-07-16 may be explained, at least in part, by alterations in these steps in the NF-κB signaling pathway leading to less NF-κB entering the nucleus and reducing the production of pro-inflammatory mediators by the activated macrophages.

核因子-κB（NF-κB）通路对于免疫系统调节和促炎信号至关重要。许多炎症性疾病和疾病，包括癌症，都与NF-κB信号传导异常有关。当巨噬细胞识别病原体的存在时，信号通路被激活，导致转录因子NF-κB的核易位，从而激活促炎基因。在这里，我们演示了新型微管解聚器NT-07-16（一种多取代的吡咯化合物）对该过程的影响。NT-07-16的处理减少了RAW264.7小鼠巨噬细胞中促炎性细胞因子的产生。看来，巨噬细胞暴露于NT-07-16后所产生的促炎性介质减少可能是由于NF-κB移位进入细胞核上游的活性所致。NF-κB易位发生在其抑制蛋白IκB-α磷酸化之后，信号提示其降解释放NF-κB，因此它可以自由移动到细胞核中。来自其他实验室的先前研究表明，这些过程与微管网络有关。我们的结果表明，暴露于微管解聚剂NT-07-16会降低IκB-α的磷酸化，还降低NF-κB与微管蛋白的缔合，这可能会影响NF-κB转运入细胞核的能力。因此，可以至少部分地解释NT-07-16的抗炎活性，