Bromodomain-containing protein 4 in inflammatory diseases: molecular mechanisms and therapeutic potential

Bromodomain-containing protein 4 (BRD4), a key member of the bromodomain and extra-terminal (BET) family, plays a critical role in regulating gene expression as an epigenetic reader. While its canonical role involves transcriptional control, BRD4 also acts as a dynamic integrator of intracellular signaling pathways and chromatin architecture, linking environmental and inflammatory stimuli to lasting gene expression changes. Recent research highlights BRD4 as a central regulator in inflammatory transcriptional networks, contributing to chronic inflammation in autoimmune diseases, cardiovascular conditions, metabolic disorders, and cancer-related inflammation. BRD4 interacts with major inflammatory transcription factors, such as NF-κB, STATs, and AP-1, amplifying transcriptional responses and maintaining an open chromatin state at super-enhancers that control inflammatory gene clusters. This has prompted interest in pharmacological strategies targeting BET proteins, with promising anti-inflammatory and antifibrotic effects in preclinical models. This review consolidates current knowledge on BRD4’s molecular mechanisms in inflammation and evaluates the potential of BET inhibitors as therapeutic agents.