Wu, Kenneth KKenneth KWuKuo, Cheng-ChinCheng-ChinKuoYet, Shaw-FangShaw-FangYetCHII-MING LEELiou, Jun-YangJun-YangLiou2023-09-142023-09-142020-07-0710217770https://www.scopus.com/record/display.uri?eid=2-s2.0-85087711541&doi=10.1186%2fs12929-020-00671-w&origin=inward&txGid=603d91f8b9c48379edd154db999c21e1https://scholars.lib.ntu.edu.tw/handle/123456789/6353695-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.en5-methoxytryptophan; Chronic renal failure; Endothelial barrier function; Heart failure; Hydroxyindole O-methyltransferase; Intimal hyperplasia; Macrophage activation; Sepsis; Smooth muscle cell migration and proliferation; Tryptophan hydroxylase-1journal article10.1186/s12929-020-00671-w326359102-s2.0-85087711541https://api.elsevier.com/content/abstract/scopus_id/85087711541