- 作者: Kenneth K. Wu, Cheng-Chin Kuo, Shaw-Fang Yet, Chii-Ming Lee and Jun-Yang Liou
- 作者服務機構: 1. Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County, 35053, Taiwan 2. College of Life Sciences, National Tsing-Hua University, Hsinchu, Taiwan 3. School of Medicine, China Medical University, Taichung, Taiwan 4. College of Medicine, National Taiwan University, Taipei, Taiwan
- 中文摘要:
- 英文摘要:
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. - 中文關鍵字:
- 英文關鍵字: 5-methoxytryptophan, Tryptophan hydroxylase-1, Hydroxyindole O-methyltransferase, Intimal hyperplasia, Endothelial barrier function, Smooth muscle cell migration and proliferation, Macrophage activation, Sepsis, Chronic renal failure, Heart failure