Indole-3-aldehyde alleviates chondrocytes inflammation through the AhR-NF-Kappa B signalling pathway

Background: Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation. Indole-3-aldehyde (3-IAld) is a tryptophan metabolite secreted by intestinal flora, which can exert anti-inflammatory effects in multiple inflammatory diseases. However, the potential therapeutic role of 3-IAld in OA and the un-derlying mechanism remain to be explored.Methods: IL-1 beta was utilized to induce chondrocytes inflammation. Then, cell counting kit-8 was carried out to assess the cytotoxicity of 3-IAld on rat chondrocytes viability. Meanwhile, RT-qPCR, Western blot, and immu-nofluorescence were performed to evaluate the expression of inflammatory factors, matrix-degrading enzymes and matrix synthesis protein, and the NF-Kappa B pathway in chondrocytes treated with IL-1 beta alone, with 3-IAld or with siRNA-AhR.Results: Our results showed that 3-IAld did not affect cellular viability at concentrations up to 50 mu M. 3-IAld significantly inhibited the expression of pro-inflammatory cytokines (IL-6, iNOS and COX-2), and matrix degrading enzymes (MMP3, MMP13 and ADAMTS5), upregulated the expression of matrix synthesis protein (aggrecan and collagen-II), and inactivated the NF-Kappa B pathway in IL-1 beta-treated chondrocytes. However, AhR knockdown could totally abolish the aforementioned therapeutic capabilities and the inactivation of the NF-Kappa B pathway induced by 3-IAld.Conclusions: 3-IAld reduced inflammation through the AhR-NF-Kappa B signalling pathway in IL-1 beta-induced chon-drocytes, which is expected to provide a new therapeutic strategy for OA.