Activation of the TLR4-JNK but not the TLR4-ERK pathway induced by indole-3-acetic acid exerts anti-proliferative effects on Caco-2 cells.

We previously found that indole-3-acetic acid (IAA) produced from tryptophan by gut microbiota decreases the expression of tumor necrosis factor α (TNFα), which is implicated in the pathogenesis of colorectal cancer (CRC). The present study aimed to determine IAA involvement in the proliferation of CRC-derived Caco-2 cells. Cell proliferation was suppressed by IAA, whereas IAA-induced aryl hydrocarbon receptor activation had no impact.

Skatole-induced p38 and JNK activation coordinately upregulates, whereas AhR activation partially attenuates TNFα expression in intestinal epithelial cells.

Increased tumor necrosis factor α (TNFα) expression in intestinal epithelial cells (IECs) plays a major role in the development and progression of inflammatory bowel disease (IBD) and colorectal cancer (CRC). The present study aimed to clarify the relationship between TNFα and skatole, a tryptophan-derived gut microbiota metabolite. The aryl hydrocarbon receptor (AhR) antagonist CH223191 promoted, whereas the p38 inhibitor SB203580 suppressed the increase in TNFα mRNA and protein expression induced by skatole in intestinal epithelial Caco-2 cells.

Suppression of TNFα expression induced by indole-3-acetic acid is not mediated by AhR activation in Caco-2 cells.

Indole-3-acetic acid (IAA) produced by intestinal bacteria from tryptophan in dietary proteins is considered to suppress the inflammatory response through aryl hydrocarbon receptor (AhR) activation. However, AhR activation was not involved in the downregulation of tumor necrosis factor α (TNFα) expression induced by IAA in Caco-2 cells. The activation of unidentified IAA receptors might attenuate the inflammatory response to TNFα in colorectal cancer cells.