Butyrate impeded the conscription of MDSCs to reduce CAC formation by blocking the TLR2 signaling pathway

Abstract

• Butyrate alleviated CAC development. • Butyrate inhibited proliferation and promoted apoptosis of CAC cells. • Butyrate inhibited the levels of MDSCs and cytokine in the TME. • Butyrate inhibited the activation of TLR2 signaling pathway. • Butyrate inhibited DSS-induced inflammation by TLR2 in Caco-2 cells. This study focuses on how butyrate alleviates CAC simulated by AOM-DSS through TLR2 signals and MDSCs, which is still unclear. Our results revealed that butyrate slowed tumorigenesis supported by remission of weight loss, survival index, DAI, pathological dysplasia, the number and size of tumors. Butyrate caused a reduction of proinflammatory factors such as IL-12, IL-6, and TNF-α as well as MDSCs that help tumor immune escape in TME. The up-regulation of TLR2/Myd88/ NF-κB in intestinal tissues of CAC was also significantly inhibited by butyrate. Besides, the inhibition of butyrate on the up -regulation of TLR2 caused by TLR2 agonist Pam3csk4 and DSS inflammatory injury in Caco-2 cells fully proved its anti-inflammatory effect through TLR2 signal pathway. So, the above results implied that by suppressing TLR2 signals, butyrate may decrease the production of IL-6, IL-12, and TNF-α to restrict the MDSCs conscription in TME and halt the CAC progression.