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. 2023 Dec 6:16:5845-5864.
doi: 10.2147/JIR.S432747. eCollection 2023.

Indole-3-Aldehyde Reduces Inflammatory Responses and Restores Intestinal Epithelial Barrier Function Partially via Aryl Hydrocarbon Receptor (AhR) in Experimental Colitis Models

Mu Wang #  1   2 , Jian Guo #  3 , Ailsa L Hart  4 , Jia V Li  1
Affiliations

Indole-3-Aldehyde Reduces Inflammatory Responses and Restores Intestinal Epithelial Barrier Function Partially via Aryl Hydrocarbon Receptor (AhR) in Experimental Colitis Models

Mu Wang et al. J Inflamm Res. .

Abstract

Purpose: Indole-3-aldehyde (IAld) has been shown to improve intestinal epithelial barrier (IEB) function through the aryl hydrocarbon receptor (AhR) in murine colitis models. However, the impact of IAld on intestinal tissue inflammation remains unexplored. This study aimed to investigate the effects of IAld on the inflammatory responses of the gut both in vivo and in vitro and probe the mechanisms by which IAld attenuates colitis.

Methods: The effects of IAld on phenotypic changes, pro-inflammatory cytokines, IEB functions and the faecal bacterial composition in mice with dextran sulfate sodium salt (DSS)-induced colitis were assessed. Macrophage cells and intestinal epithelial cells were stimulated with lipopolysaccharide (LPS), and the effects of IAld on the inflammatory responses and IBE functions were measured.

Results: IAld reduced IL-6, IL-1β and TNF-α protein levels in both colonic tissues from the mice with colitis and LPS-stimulated macrophage cells. The IAld-mediated reduction of IL-6 but not IL-1β and TNF-α was through AhR activation. Furthermore, nuclear factor-κB pathway was found to be inhibited by IAld treatment via AhR activation both in vivo and in vitro. Gut permeability was significantly improved by IAld in both DSS-treated mice and LPS-stimulated Caco-2 cells. This observation is consistent with downregulation of phosphorylated myosin light chain through AhR activation. IAld did not appear to have an effect on the bacterial composition in mice with colitis despite the reduced colonic inflammatory responses.

Conclusion: IAld improved DSS-induced colitis by inhibiting the inflammatory responses and restoring IEB function, partially via AhR activation. This work provided insight into the function of IAld in modulating gut inflammation.

Keywords: indole-3-aldehyde aryl hydrocarbon receptor intestinal inflammation.

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Conflict of interest statement

The authors report no conflicts of interest in this work. Jia Li declared consultancy work for the University of Cardiff, the work is not relevant to the submitted manuscript.

Figures

None
Graphical abstract
Figure 1
Figure 1
Experimental schedule and effects of IAld supplementation on basic indicators in a DSS-induced colitis mouse model.
Figure 2
Figure 2
Effects of IAld supplementation on gut barrier integrity in a DSS-induced mouse model.
Figure 3
Figure 3
The effects of different concentrations of IAld on decreasing the level of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS stimulated RAW264.7 cells.
Figure 4
Figure 4
IAld activated AhR signalling in the different cell types.
Figure 5
Figure 5
IAld decreased proinflammatory cytokine expression in LPS-stimulated macrophages partially through AhR.
Figure 6
Figure 6
IAld suppressed NF-κB and JNK pathway through AhR in macrophage cells.
Figure 7
Figure 7
IAld attenuated Caco-2 epithelial barrier dysfunction through AhR activation.
Figure 8
Figure 8
IAld supressed NF-κB through AhR in Caco-2 cells.
Figure 9
Figure 9
Effects of IAld and AhR activation on the gut microbiome composition in a DSS-induced mouse model.
See this image and copyright information in PMC

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