Department of Biology Education, College of Education, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Cell Immunol. 2013 Jul-Aug;284(1-2):139-45. doi: 10.1016/j.cellimm.2013.07.014. Epub 2013 Aug 2.
Once activated by an infected pathogen, dendritic cells (DC's) migrate toward secondary lymphoid organs, and release inflammatory mediators. Therefore, in some case, mature DC's (mDC's) are considered to be potent inflammatory inducers. In this study we demonstrated that histone acetylation plays an important regulatory role in conserving the migration activity of the DC's. We showed that histone deacetylase (HDAC) inhibition reduces CXC chemokine receptor 4 (CXCR4)-dependent DC's migration. These inhibitory effects were found to be caused by a reduction in the expression of CXCR4, and by the phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 (ERK 1/2), and c-Jun N-terminal kinase (JNK). Taken together, histone deacetylase inhibitors (HDACi's) inhibit the phosphorylation of MAP kinases, and this inhibition reduces the expression of CXCR4, and this reduction decreases the chemotactic activity of mDC's.
一旦被感染的病原体激活，树突状细胞（DC）就会向次级淋巴器官迁移，并释放炎症介质。因此，在某些情况下，成熟的 DC（mDC）被认为是强有力的炎症诱导剂。在这项研究中，我们证明了组蛋白乙酰化在维持 DC 迁移活性方面起着重要的调节作用。我们表明，组蛋白去乙酰化酶（HDAC）的抑制减少了 CXC 趋化因子受体 4（CXCR4）依赖性 DC 的迁移。这些抑制作用是由于 CXCR4 的表达减少，以及 p38 丝裂原活化蛋白激酶（MAPK）、细胞外信号调节激酶 1 和 2（ERK1/2）和 c-Jun N 端激酶（JNK）的磷酸化减少所致。总之，组蛋白去乙酰化酶抑制剂（HDACi）抑制 MAP 激酶的磷酸化，这种抑制作用减少了 CXCR4 的表达，而这种减少降低了 mDC 的趋化活性。
