Frontiers in immunology · 2026
CU104, a novel barrier function enhancer, improves colitis via modulation of barrier function and immune cell recruitment.
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Park I Seul, Kim Ji Hyung, Kim Dongyeop, Kim Ye Won, Shin Yoojin, Kim Ki Beom, Zhang Haiying, Kim Tae Il, Kim Seung Won, Kwon Young-Guen, Cheon Jae Hee
Аннотация
BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic and relapsing condition with complex pathogenesis and limited therapeutic options. The efficacy of CU104, a novel blocker of endothelial dysfunction, in IBD models is poorly understood. Moreover, its precise cellular or molecular mechanisms in colitis remain unknown.
METHODS: To evaluate the therapeutic potential of CU104, we tested CU104 in two colitis models: dinitrobenzene sulfonic acid (DNBS)-induced colitis in wild-type mice and dextran sodium sulfate (DSS)-challenged colitis in IL-10 knockout mice. Additionally, we used Caco-2, HCT-116, and HT-29 cells to assess CU104 effects on intestinal barrier function (FITC-dextran permeability and TEER), inflammatory signaling (reporter assays), actin dynamics, and gene expression (gene expression profiling and immune assays).
RESULTS: CU104 demonstrated potent suppressive effects on innate immune responses, intestinal and vascular barrier dysfunctions, and immune cell recruitment in these colitis models. Furthermore, CU104 inhibited the activation of the transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells and interferon regulatory factor, as well as the ezrin/radixin/moesin (ERM) signaling pathway, both in vitro and in vivo, by modulating actin dynamics. Consistent with these findings, CU104 improved the functions of vascular and intestinal barriers and regulated immune cell recruitment during inflammation.
CONCLUSIONS: Collectively, our findings demonstrate that CU104 can regulate actin dynamics and inflammatory signaling pathways, highlighting potential therapeutic targets for IBD.
METHODS: To evaluate the therapeutic potential of CU104, we tested CU104 in two colitis models: dinitrobenzene sulfonic acid (DNBS)-induced colitis in wild-type mice and dextran sodium sulfate (DSS)-challenged colitis in IL-10 knockout mice. Additionally, we used Caco-2, HCT-116, and HT-29 cells to assess CU104 effects on intestinal barrier function (FITC-dextran permeability and TEER), inflammatory signaling (reporter assays), actin dynamics, and gene expression (gene expression profiling and immune assays).
RESULTS: CU104 demonstrated potent suppressive effects on innate immune responses, intestinal and vascular barrier dysfunctions, and immune cell recruitment in these colitis models. Furthermore, CU104 inhibited the activation of the transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells and interferon regulatory factor, as well as the ezrin/radixin/moesin (ERM) signaling pathway, both in vitro and in vivo, by modulating actin dynamics. Consistent with these findings, CU104 improved the functions of vascular and intestinal barriers and regulated immune cell recruitment during inflammation.
CONCLUSIONS: Collectively, our findings demonstrate that CU104 can regulate actin dynamics and inflammatory signaling pathways, highlighting potential therapeutic targets for IBD.