Panobinostat suppresses cGAS-STING pathway activation and ameliorates DSS-induced colitis in mice.

Abnormal or excessive activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in natural immunity nucleic acid sensing causing the overproduction of cytokines, triggering inflammatory tissue damage, immune pathology, or autoimmune diseases closely associated with the release of type I interferons. Inhibiting aberrant cGAS activation represents a promising therapeutic strategy for clinical development. Through screening a library of epigenetic drugs, we identified that the histone deacetylase inhibitor panobinostat significantly suppresses the cGAS-STING pathway, reducing both the mRNA expression and protein phosphorylation levels of downstream inflammatory mediators, as well as decreasing the secretion of inflammatory factors. Furthermore, we found that panobinostat alleviates symptoms of dextran sulfate sodium-induced colitis in mice, offering new insights into the prevention and treatment of inflammatory diseases.