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Войти в исследования Molecular biology reports · 2026
Attenuation of IL-8 expression following AHR inhibition in an in vitro model of intestinal inflammation.
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Parsamanesh Gilda, Noorbakhsh Farshid, Baghaei Kaveh, Rezaei Nima
Аннотация
BACKGROUND: The aryl hydrocarbon receptor (AHR) is an important regulator of intestinal homeostasis and has been linked to inflammatory bowel disease (IBD). However, its role in epithelial inflammatory responses is not fully understood. This study aimed to evaluate AHR signaling in in vitro models of intestinal inflammation and to investigate the effects of pharmacological AHR inhibition.
METHODS: Two inflammatory models were evaluated: a differentiated Caco-2/THP-1 co-culture system and a TNF-α/LPS-stimulated Caco-2 epithelial model. AHR expression was measured by real-time PCR. The model showing an AHR expression pattern consistent with our previous findings in pediatric IBD tissues was selected for further experiments. AHR was inhibited using BAY2416964, and the expression of TIPARP, IL-8, IL-6, and TNF-α was evaluated. IL-8 protein levels were also measured by ELISA.
RESULTS: AHR expression was significantly reduced in the Caco-2/THP-1 co-culture model but increased following TNF-α/LPS stimulation. Therefore, the TNF-α/LPS-stimulated Caco-2 model was selected for further experiments. BAY2416964 significantly reduced TIPARP expression, supporting effective inhibition of AHR signaling. AHR inhibition significantly reduced IL-8 mRNA expression, while reductions in IL-6 and TNF-α did not reach statistical significance. At the protein level, TNF-α/LPS significantly increased IL-8 production. BAY2416964 reduced IL-8 protein levels, although this reduction did not reach statistical significance.
CONCLUSIONS: These findings suggest that AHR contributes to inflammatory responses in intestinal epithelial cells. Among the inflammatory mediators examined, IL-8 showed the most consistent response to AHR inhibition in this experimental model. The findings extend our previous observations of altered AHR expression by providing functional evidence for its involvement in epithelial inflammatory signaling. Further studies using complementary approaches and more physiologically relevant models are needed to define the broader functional significance of AHR inhibition in intestinal inflammation.
METHODS: Two inflammatory models were evaluated: a differentiated Caco-2/THP-1 co-culture system and a TNF-α/LPS-stimulated Caco-2 epithelial model. AHR expression was measured by real-time PCR. The model showing an AHR expression pattern consistent with our previous findings in pediatric IBD tissues was selected for further experiments. AHR was inhibited using BAY2416964, and the expression of TIPARP, IL-8, IL-6, and TNF-α was evaluated. IL-8 protein levels were also measured by ELISA.
RESULTS: AHR expression was significantly reduced in the Caco-2/THP-1 co-culture model but increased following TNF-α/LPS stimulation. Therefore, the TNF-α/LPS-stimulated Caco-2 model was selected for further experiments. BAY2416964 significantly reduced TIPARP expression, supporting effective inhibition of AHR signaling. AHR inhibition significantly reduced IL-8 mRNA expression, while reductions in IL-6 and TNF-α did not reach statistical significance. At the protein level, TNF-α/LPS significantly increased IL-8 production. BAY2416964 reduced IL-8 protein levels, although this reduction did not reach statistical significance.
CONCLUSIONS: These findings suggest that AHR contributes to inflammatory responses in intestinal epithelial cells. Among the inflammatory mediators examined, IL-8 showed the most consistent response to AHR inhibition in this experimental model. The findings extend our previous observations of altered AHR expression by providing functional evidence for its involvement in epithelial inflammatory signaling. Further studies using complementary approaches and more physiologically relevant models are needed to define the broader functional significance of AHR inhibition in intestinal inflammation.