Therapeutic effects of D-cycloserine in mouse models of IBD and CAC: Targeting NLRP3 inflammasome and intestinal barrier integrity
Chen, Shengwei, Yan, Lizhuowen, Zeng, Jingtao, Meng, Wei, Zhuang, Jionghan, Chen, Fengying, Guo, Yonglong, Abd El-Aty, A. M., Ju, Xianghong, Yang, Shihua
D-Cycloserine (DCS), a broad-spectrum antibiotic and NMDA receptor modulator, exhibits immunomodulatory effects beyond its known neurological and antimicrobial functions. This study investigated DCS's therapeutic potential in inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC) using in vitro and in vivo models. In lipopolysaccharide (LPS)-stimulated NCM460 cells, DCS inhibited NLRP3 inflammasome activation and restored tight junction protein expression. In dextran sulfate sodium (DSS)-induced murine colitis, both preventive and therapeutic DCS regimens attenuated inflammation, reduced histopathological damage, and preserved intestinal barrier integrity. In azoxymethane (AOM)/DSS-induced CAC, DCS decreased tumor burden and reduced Ki-67+ cell proliferation without systemic toxicity. These findings position DCS as a promising dual-target candidate for IBD and CAC management through NLRP3-caspase-1-GSDMD pathway inhibition and epithelial barrier maintenance.
- Dergi
- INTERNATIONAL IMMUNOPHARMACOLOGY
- Yıl
- 2025
- Cilt
- 163
- ISSN
- 1567-5769
- eISSN
- 1878-1705
- DOI
- 10.1016/j.intimp.2025.115209
- WoS UID
- WOS:001539289500001