Therapeutic effects of D-cycloserine in mouse models of IBD and CAC: Targeting NLRP3 inflammasome and intestinal barrier integrity

Chen S., Yan L., Zeng J., Meng W., Zhuang J., Chen F., ...Daha Fazla

International Immunopharmacology, cilt.163, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 163
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.intimp.2025.115209
  • Dergi Adı: International Immunopharmacology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: CAC, D-cycloserine, IBD, NLRP3-caspase1-GSDMD, Tight junction proteins
  • Atatürk Üniversitesi Adresli: Evet

Özet

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.