5-methoxytryptophan: an arsenal against vascular injury and inflammation

• Main Authors: Kenneth K. Wu, Cheng-Chin Kuo, Shaw-Fang Yet, Chii-Ming Lee, Jun-Yang Liou
• Format: Article
• Language: English
• Published: BMC 2020-07-01
• Series: Journal of Biomedical Science
• Subjects: 5-methoxytryptophan; Tryptophan hydroxylase-1; Hydroxyindole O-methyltransferase; Intimal hyperplasia; Endothelial barrier function; Smooth muscle cell migration and proliferation
• Online Access: http://link.springer.com/article/10.1186/s12929-020-00671-w

Abstract 5-methoxytryptophan (5-MTP) is an endothelial factor with anti-inflammatory properties. It is synthesized from L-tryptophan via two enzymatic steps: tryptophan hydroxylase-1 (TPH-1) and hydroxyindole O-methyltransferase. Lipopolysaccharide (LPS) and pro-inflammatory cytokines suppress endothelial 5-MTP production by inhibiting TPH-1 expression. 5-MTP protects endothelial barrier function and promotes endothelial repair, while it blocks vascular smooth muscle cell migration and proliferation by inhibiting p38 MAPK activation. 5-MTP controls macrophage transmigration and activation by inhibiting p38 MAPK and NF-κB activation. 5-MTP administration attenuates arterial intimal hyperplasia, defends against systemic inflammation and prevents renal fibrosis in relevant murine models. Serum 5-MTP level is depressed in human sepsis as well as in mice with sepsis-like disorder. It is reduced in chronic kidney disease and acute myocardial infarction in humans. The reported data suggest that serum 5-MTP may be a theranostic biomarker. In summary, 5-MTP represents a new class of tryptophan metabolite which defends against inflammation and inflammation-mediated tissue damage and fibrosis. It may be a valuable lead compound for developing new drugs to treat complex human inflammatory disorders.