2. Academic Validation
  3. Panobinostat suppresses cGAS-STING pathway activation and ameliorates DSS-induced colitis in mice

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

  • Int Immunopharmacol. 2025 Oct 10:167:115637. doi: 10.1016/j.intimp.2025.115637.
Meizhen Qin 1,  Zijiao Liu 2,  Meng Wang 3,  Wanqing Yang 4,  Zihua Zhou 5,  Mengfei Xue 6,  Fan Xia 7,  Chunyong Ding 8,  Ao Zhang 5,  Zhenliang Sun 9
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 2 School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; Zhaoqing University, Zhaoqing 526061, China.
  • 3 Department of Clinical Laboratory, Shanghai Zhongye Hospital, Shanghai 200941, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 4 School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 5 Shanghai Frontiers Science Center of Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 6 The South Campus of the Sixth People's Hospital Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai 201499, China.
  • 7 Shanghai Medical College of Fudan University, Shanghai 200032,China.
  • 8 Shanghai Frontiers Science Center of Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: chunding@sjtu.edu.cn.
  • 9 The South Campus of the Sixth People's Hospital Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai 201499, China. Electronic address: zhenliang6@126.com.
PMID: 41075748 DOI: 10.1016/j.intimp.2025.115637
Abstract

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.

Keywords

Cytokine expression; DSS-induced colitis; HDAC inhibitor; Inflammatory bowel disease; Innate immunity; Panobinostat; cGAS-STING pathway.

Figures
Products