Induction Of NO Metabolism In Enterocytes Alleviates Colitis And Inflammation-Associated Colon Cance

[Mito]

Induction of Nitric-Oxide Metabolism in Enterocytes Alleviates Colitis and Inflammation-Associated Colon Cancer

https://www.cell.com/cell-reports/pdf/S2211-1247(18)30612-0.pdf

Highlights

• ASL CKO enables dissection of NO contribution to disease in a cell-specific manner
• NO has different roles in the specific cell types relevant to colitis
  
• NO synthesis in enterocytes is a native defense mechanism against colitis
  
• Metabolic modulation of NO levels is beneficial for colitis and associated colon cancer

“Broadly, our study serves as a proof of concept for three main ideas. First, it confirms that regulating ASL allows metabolic regulation of NO in a cell-specific manner. Second, it shows that, during disease, cell-autonomous production of NO by iNOS can be protective as part of the intestinal innate immune response. Last, our study demonstrates the superior metabolic advantage of supplementing with substrates and upregulating the relevant metabolic enzymes over giving the deficient molecule directly as therapy. Because both citrulline and fisetin are nutraceutical agents that are available as supplements, the findings from this study could be translated rather straightforward into the human context.”