Work

Modulation of occludin, NF-κB, p-STAT3, and Th17 response by DJ-X-025 decreases inflammation and ameliorates experimental colitis 2378

Year: 2025

Type: article

Abstract: Description Inflammatory bowel disease (IBD) involves a range of immune-mediated disorders marked by systemic and local intestinal inflammation. In this study, we developed a compound, DJ-X-025, and explored its anti-inflammatory effects using in vitro lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and an in vivo dextran sodium sulfate (DSS)-induced colitis. DJ-X-025 treatment markedly altered the morphology of LPS-treated RAW 264.7 macrophages from elongated to round shapes and reduced the level of inflammatory markers like TNF-α, IL-1β, IL-6, and iNOS. Further, we observed that DJ-X-025 was steered to improve colon length, muscularis mucosa thickness, and colon inflammatory score compared to the DSS group alone. DJ-X-025 effectively inverted the increased population of activated T cells, Th17, and macrophages in lamina propria by DSS treatment, leading to a substantial reduction in the inflammatory response in the colon. Strikingly, DJ-X-025 treatment enhanced the expression of occludin and diminished the expression of NF-κB and phosphorylation of STAT3 in the colon of DSS-treated mice compared to DSS-alone. Additionally, DJ-X-025 induced the expression of FOXP3 in the colon and, reduced systemic inflammatory cytokine/chemokine levels further supporting its immunomodulatory effects. Collectively, these findings suggest that DJ-X-025 induces colon occludin and suppresses NF-κB, p-STAT3, and Th17 response, thus might be a promising therapeutic agent for the treatment of IBD. Funding Sources Supported by NIH grant R01 AI140405 Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.303