Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
J Dent Res. 2010 May;89(5):430-44. doi: 10.1177/0022034510366813. Epub 2010 Mar 26.
Hypoxia is an integral component of the inflamed tissue microenvironment. Today, the influence of hypoxia on the natural evolution of inflammatory responses is widely accepted; however, many molecular and cellular mechanisms mediating this relationship remain to be clarified. Hypoxic stress affects several independent transcriptional regulators related to inflammation in which HIF-1 and NF-kappaB play central roles. Transcription factors interact with both HATs and HDACs, which are components of large multiprotein co-regulatory complexes. This review summarizes the current knowledge on hypoxia-responsive transcriptional pathways in inflammation and their importance in the etiology of chronic inflammatory diseases, with the primary focus on transcriptional co-regulators and histone modifications in defining gene-specific transcriptional responses in hypoxia, and on the recent progress in the understanding of hypoxia-mediated epigenetic reprogramming. Furthermore, this review discusses the molecular cross-talk between glucocorticoid anti-inflammatory pathways and hypoxia.
缺氧是炎症组织微环境的一个组成部分。如今，缺氧对炎症反应自然演变的影响已被广泛接受；然而，许多介导这种关系的分子和细胞机制仍有待阐明。缺氧应激影响与炎症相关的几个独立的转录调控因子，其中 HIF-1 和 NF-κB 起着核心作用。转录因子与 HAT 和 HDAC 相互作用，HAT 和 HDAC 是大型多蛋白共调节复合物的组成部分。这篇综述总结了目前关于炎症中缺氧反应性转录途径的知识，以及它们在慢性炎症性疾病发病机制中的重要性，主要集中在转录共调节剂和组蛋白修饰在缺氧条件下定义基因特异性转录反应，以及在理解缺氧介导的表观遗传重编程方面的最新进展。此外，这篇综述还讨论了糖皮质激素抗炎途径与缺氧之间的分子相互作用。
