Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, PR China.
Biochem Biophys Res Commun. 2012 Jan 13;417(2):777-83. doi: 10.1016/j.bbrc.2011.12.034. Epub 2011 Dec 16.
We showed previously that calcineurin B subunit (CnB) could inhibit S180 solid tumor growth in mice and prolong the survival of mice bearing H22 ascites tumors, but the underlying antitumor mechanism remained unclear. Here, we report that the calcineurin B subunit binds to CD11b on RAW264.7 macrophages and induces TRAIL expression and NF-κB activation in a dose and time dependent manner, and that CnB-induced TRAIL expression and NF-κB activation are both dependent on this CD11b. Furthermore, CnB-induced TRAIL expression is mediated by NF-κB. These findings reveal a novel signaling pathway (CnB-CD11b-NF-κB-TRAIL) regulating TRAIL expression and may help to understand the roles of the calcineurin B subunit in the regulation of innate immunity.
我们之前已经表明，钙调神经磷酸酶 B 亚基（CnB）可以抑制小鼠 S180 实体瘤的生长，并延长荷瘤 H22 腹水瘤小鼠的存活时间，但潜在的抗肿瘤机制尚不清楚。在这里，我们报告钙调神经磷酸酶 B 亚基与 RAW264.7 巨噬细胞上的 CD11b 结合，并以剂量和时间依赖的方式诱导 TRAIL 表达和 NF-κB 激活，而 CnB 诱导的 TRAIL 表达和 NF-κB 激活均依赖于这种 CD11b。此外，CnB 诱导的 TRAIL 表达是由 NF-κB 介导的。这些发现揭示了一条调节 TRAIL 表达的新信号通路（CnB-CD11b-NF-κB-TRAIL），并可能有助于理解钙调神经磷酸酶 B 亚基在固有免疫调节中的作用。
