Figure 3.

Potential pathological and therapeutic consequences of modulating histone deacetylase activity in rheumatoid arthritis. Depressed histone deacetylase (HDAC) activity relative to histone acetyl transferase (HAT) activity in rheumatoid arthritis (RA) synovial tissue might promote chromatin relaxation and activation of inflammatory transcription factors (TF). Moreover, depressed HDAC activity may decrease patient responsiveness to glucocorticoid (GC) treatment. The therapeutic application of HDAC agonists may decrease inflammation by promoting chromatin condensation and/or deacetylating TF at sites required for DNA binding. Additionally, patients may respond better to GC therapy. Therapeutic application of HDAC inhibitors might demonstrate clinical benefits by preventing deacetylation of TF at sites required for their activation, or inducing transcription of genes promoting cell cycle arrest or apoptosis. HDAC inhibitors, however, might render RA patients refractory to concomitant GC therapy. Ac, acetylation.