Indole 3 propionic acid exerts anti inflammatory effects by inhibiting NFkB via the noncanonical AhR pathway in human gut skin and airway epithelium
World Immune Regulation Meeting – XX, Chur, İsviçre, 11 - 14 Mart 2026, ss.30, (Özet Bildiri)
- Yayın Türü: Bildiri / Özet Bildiri
- Basıldığı Şehir: Chur
- Basıldığı Ülke: İsviçre
- Sayfa Sayıları: ss.30
- Bursa Uludağ Üniversitesi Adresli: Evet
Özet
Epithelial barrier dysfunction and inflammation are central features of many diseases affecting the skin, gut, and airways. We demonstrate that indole-3-propionic acid (IPA), a microbial tryptophan metabolite, accelerates the development and strengthens the integrity of the gut epithelial barrier and exerts anti-inflammatory effects in gut-on-a-chip 3D cultures. The application of 0.25, 1- and 4-mM doses of IPA significantly from apical surface increased the gut epithelial barrier integrity compared to control by almost 2 times up to 800 ohm x cm2 during the development phase of the gut epithelial barrier. The transcriptomic analysis showed that it upregulates gene expression associated with xenobiotic metabolism, ion transport, water transport, glucose transport, and amino acid transport pathways. It increases the tight junction protein claudin-1 gene expression. IPA showed an anti-inflammatory activity, as demonstrated with decreased chemokines (CXCL-5,10 and 11, CCL-20,23 and 25, CSF-1 and MCP-1) and IL-1a levels in culture medium detected by proximity extension assay. Further in the skin and airways, it significantly reduced pro-inflammatory cytokines and chemokines at physiologically relevant serum concentrations. IPA counteracted tumor necrosis factor (TNF)-induced epithelial barrier disruption and inflammation across all three tissue types, as demonstrated in ex vivo human skin gut-on-a-chip assays and nasal epithelial spheroid cultures. Mechanistically, IPA inhibited NF-kappaB signaling, acting as a partial agonist of the aryl hydrocarbon receptor (AhR), as confirmed by reporter assays, transcriptomic profiling, and CYP1A1 expression. Importantly, knockdown of AhR and its partner ARNT reveals that IPA’s anti-inflammatory action is mediated via the noncanonical AhR pathway. Furthermore, IPA inhibited AhR nuclear translocation in the same way as canonical AhR antagonists. These findings identify IPA as a promising therapeutic candidate for inflammatory and barrier-disruptive conditions of the skin, gut, and airways.