NF-κB1 (p50) homodimers differentially regulate pro- and anti-inflammatory cytokines in macrophages
NF-κB1 (p50) homodimers differentially regulate pro- and anti-inflammatory cytokines in macrophages
复制标题
DOI：
10.1074/jbc.m602222200
复制
发表时间：
2006-09-08
影响因子：
4.8
通讯作者：
Mosser, David M.
中科院分区：
文献类型：
--
作者：
Cao, Shanjin;Zhang, Xia;Mosser, David M.
核因子-kappaB/Rel是一个转录因子家族，其激活与炎性细胞因子的产生有关。在这里，我们研究了核因子-kappaB信号在抗炎细胞因子白介素10(IL-10)调节中的作用。我们确定了单个核因子-kappa B家族成员--核因子-kappa B1(P50)在促进IL-10转录中的作用。IL-10近端启动子上的核因子-kappaB顺式元件位于-55/-46，其中p50可与转录共激活因子CREB结合蛋白同源二聚并形成复合体来激活转录。其他REL家族成员在IL-10转录中的作用似乎微乎其微。缺乏p50的小鼠更容易发生致死性内毒素血症，p50(-/)小鼠的巨噬细胞对脂多糖的细胞因子反应偏斜，其特征是IL-10降低，肿瘤坏死因子和IL-12升高。综上所述，我们的研究表明，核因子-kappa B1(P50)同源二聚体可以作为IL-10的转录激活剂。核因子-kappa B_1(P50)对促炎和抗炎细胞因子产生的相互调节可能为控制先天免疫反应提供潜在的新途径。
NF-kappa B/Rel is a family of transcription factors whose activation has long been linked to the production of inflammatory cytokines. Here, we studied NF-kappa B signaling in the regulation of the anti-inflammatory cytokine, interleukin-10 (IL-10). We identified a role for a single NF-kappa B family member, NF-kappa B1 (p50), in promoting the transcription of IL-10. The NF-kappa B cis-element on IL-10 proximal promoter was located to -55/-46, where p50 can homodimerize and form a complex with the transcriptional co-activator CREB-binding protein to activate transcription. The other Rel family members appear to play a negligible role in IL-10 transcription. Mice lacking p50 were more susceptible to lethal endotoxemia, and macrophages taken from p50(-/)-mice exhibit skewed cytokine responses to lipopolysaccharide, characterized by decreased IL-10 and increased tumor necrosis factor and IL-12. Taken together, our studies demonstrate that NF-kappa B1 (p50) homodimers can be transcriptional activators of IL-10. The reciprocal regulation of pro-and anti-inflammatory cytokine production by NF-kappa B1 (p50) may provide potential new ways to manipulate the innate immune response.