Epigenetic regulation of CC-chemokine ligand 2 in nonresolving inflammation.
Epigenetic regulation of CC-chemokine ligand 2 in nonresolving inflammation.
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DOI：
10.1515/bmc-2014-0022
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发表时间：
2014-08-01
影响因子：
--
通讯作者：
Kishioka, Shiroh
中科院分区：
文献类型：
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作者：
Kiguchi, Norikazu;Saika, Fumihiro;Kishioka, Shiroh
由白细胞和驻留组织细胞之间的串扰介导的炎症对于维持稳态至关重要。由于趋化因子配体和受体广泛分布于组织中，可以募集各种白细胞，因此了解炎症性疾病的调节机制非常重要。趋化因子如CC-趋化因子配体2（CCL 2）在循环白细胞募集后通过趋化因子-细胞因子网络放大和维持炎症。趋化因子依赖性非消退性炎症发生在外周和中枢神经系统，并且是包括癌症和神经性疼痛在内的几种难治性疾病的基础。趋化因子的慢性上调通常由DNA甲基化、组蛋白修饰和核小体定位组成的表观遗传机制介导。特别是，组蛋白乙酰化和甲基化已被证明在趋化因子表达的上调中起重要作用。除了CCL 2，其他几种趋化因子通过表观遗传诱导强烈促进神经性疼痛。因此，靶向表观遗传变化可能对非消退性炎症性疾病如神经性疼痛具有治疗潜力。对炎症性疾病表观遗传学的进一步研究将促进难治性炎症性疾病新的有效治疗策略的发展。
Inflammation mediated by the crosstalk between leukocytes and resident tissue cells is crucial for the maintenance of homeostasis. Because chemokine ligands and receptors, which recruit a variety of leukocytes, are widely distributed among tissues, it is important to understand the mechanisms regulating inflammatory disease. Chemokines such as CC-chemokine ligand 2 (CCL2) amplify and maintain inflammation through chemokine-cytokine networks after the recruitment of circulating leukocytes. Chemokine-dependent nonresolving inflammation occurs in the peripheral and central nervous systems, and underlies several intractable diseases, including cancer and neuropathic pain. The chronic upregulation of chemokines is often mediated by epigenetic mechanisms consisting of DNA methylation, histone modification, and nucleosome positioning. In particular, histone acetylation and methylation have been shown to play important roles in the upregulation of chemokine expression. In addition to CCL2, several other chemokines strongly contribute to neuropathic pain through epigenetic induction. Consequently, targeting epigenetic changes may have therapeutic potential for nonresolving inflammatory diseases such as neuropathic pain. Further research into the epigenetics of inflammatory diseases should promote the development of novel and effective treatment strategies for intractable inflammatory diseases.