P300 in Inflammation: An Updated Perspective on Its Molecular Mechanisms and Therapeutic Potential

Transcription cofactor p300 is characterized by histone acetyltransferase (HAT) activity, which endows p300 with dual functions of chromatin remodeling and gene transcription and participates in regulating various basic cellular functions. P300 mainly enhances the expression of downstream pro-inflammatory factors such as TNF-α and IL-6 by acetylating core transcription factors in the inflammatory signaling pathway, such as NF-κB and JAK/STAT. P300 also reshapes the epigenetic profile of important cellular components in inflammation, such as macrophages or T cells, by mediating histone H3K27ac modification. Based on the above molecular mechanisms, p300 plays a key role in various inflammatory diseases, including respiratory inflammatory, autoimmune, metabolic-related and neuroinflammatory diseases as well as infectious inflammation. Small molecule inhibitors targeting p300 show anti-inflammatory potential in various preclinical animal models; however, their tissue-specific targeting mechanisms and long-term safety need further exploration. The current review summarizes the molecular mechanism basis, cell specific functions, and targeted intervention strategies of p300 in inflammatory diseases, and explores the development of novel p300-based anti-inflammatory medication.