Transcriptome Remodeling in Hypoxic Inflammation

Abstract

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-κB 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.