Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer [Research]

Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)–induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2–/–) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2–/– colon tissue, and demonstrated attenuation of the elevation of both inflammation-related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation. After undergoing transplantation of wild-type bone marrow, SMS2–/– mice also exhibited inhibition of DSS-induced inflammation in the colon, which suggested that SMS2 deficiency in bone marrow–derived immune cells was not involved in the inhibition of colitis. Finally, in an azoxymethane/DSS-induced cancer model, SMS2 deficiency significantly decreased tumor incidence in the colon. Our results demonstrate that SMS2 deficiency inhibits DSS-induced colitis and subsequent colitis-associated colon cancer via inhibition of colon epithelial cell–mediated inflammation; therefore, inhibition of SMS2 may be a potential therapeutic targe...
Source: FASEB Journal - Category: Biology Authors: Tags: Research Source Type: research