Evidence map›Paper›PMID 27151398›Full record

ArticleCirculation research2016

Endothelium-Derived 5-Methoxytryptophan Is a Circulating Anti-Inflammatory Molecule That Blocks Systemic Inflammation.

Yi-Fu Wang, Yu-Juei Hsu, Hsu-Feng Wu, Guan-Lin Lee, Ya-Sung Yang, Jing-Yiing Wu, Shaw-Fang Yet, Kenneth K Wu, Cheng-Chin Kuo

Erratum issuedOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
4.0field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 94 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Yi-Fu WangFrom the Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (Y.-F.W., H.-F.W., G.-L.L., J.-Y.W., S.-F.Y., K.K.W., C.-C.K.); Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan (Y.-F.W.); Division of Nephrology (Y.-J.H.), Division of Infectious Diseases and Tropical Medicine (Y.-S.Y.), Department of Medicine, Tri-Service General Hospital (Y.-J.H., Y.-S.Y.), and Graduate Institutes of Life Sciences and Biochemistry (Y.-J.H., G.-L.L., Y.-S.Y., C.-C.K.), National Defense Medical Center, Taipei, Taiwan; Metabolomic Research Center, China Medical University Hospital (S.-F.Y., K.K.W., C.-C.K.) and Graduate Institute of Basic Medical Science (S.-F.Y., K.K.W., C.-C.K.), China Medical University, Taichung, Taiwan; and Department of Medicine, University of Texas, Houston (K.K.W.).
Yu-Juei HsuFrom the Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (Y.-F.W., H.-F.W., G.-L.L., J.-Y.W., S.-F.Y., K.K.W., C.-C.K.); Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan (Y.-F.W.); Division of Nephrology (Y.-J.H.), Division of Infectious Diseases and Tropical Medicine (Y.-S.Y.), Department of Medicine, Tri-Service General Hospital (Y.-J.H., Y.-S.Y.), and Graduate Institutes of Life Sciences and Biochemistry (Y.-J.H., G.-L.L., Y.-S.Y., C.-C.K.), National Defense Medical Center, Taipei, Taiwan; Metabolomic Research Center, China Medical University Hospital (S.-F.Y., K.K.W., C.-C.K.) and Graduate Institute of Basic Medical Science (S.-F.Y., K.K.W., C.-C.K.), China Medical University, Taichung, Taiwan; and Department of Medicine, University of Texas, Houston (K.K.W.).
Hsu-Feng WuFrom the Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (Y.-F.W., H.-F.W., G.-L.L., J.-Y.W., S.-F.Y., K.K.W., C.-C.K.); Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan (Y.-F.W.); Division of Nephrology (Y.-J.H.), Division of Infectious Diseases and Tropical Medicine (Y.-S.Y.), Department of Medicine, Tri-Service General Hospital (Y.-J.H., Y.-S.Y.), and Graduate Institutes of Life Sciences and Biochemistry (Y.-J.H., G.-L.L., Y.-S.Y., C.-C.K.), National Defense Medical Center, Taipei, Taiwan; Metabolomic Research Center, China Medical University Hospital (S.-F.Y., K.K.W., C.-C.K.) and Graduate Institute of Basic Medical Science (S.-F.Y., K.K.W., C.-C.K.), China Medical University, Taichung, Taiwan; and Department of Medicine, University of Texas, Houston (K.K.W.).
Guan-Lin LeeFrom the Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (Y.-F.W., H.-F.W., G.-L.L., J.-Y.W., S.-F.Y., K.K.W., C.-C.K.); Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan (Y.-F.W.); Division of Nephrology (Y.-J.H.), Division of Infectious Diseases and Tropical Medicine (Y.-S.Y.), Department of Medicine, Tri-Service General Hospital (Y.-J.H., Y.-S.Y.), and Graduate Institutes of Life Sciences and Biochemistry (Y.-J.H., G.-L.L., Y.-S.Y., C.-C.K.), National Defense Medical Center, Taipei, Taiwan; Metabolomic Research Center, China Medical University Hospital (S.-F.Y., K.K.W., C.-C.K.) and Graduate Institute of Basic Medical Science (S.-F.Y., K.K.W., C.-C.K.), China Medical University, Taichung, Taiwan; and Department of Medicine, University of Texas, Houston (K.K.W.).
Ya-Sung YangFrom the Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (Y.-F.W., H.-F.W., G.-L.L., J.-Y.W., S.-F.Y., K.K.W., C.-C.K.); Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan (Y.-F.W.); Division of Nephrology (Y.-J.H.), Division of Infectious Diseases and Tropical Medicine (Y.-S.Y.), Department of Medicine, Tri-Service General Hospital (Y.-J.H., Y.-S.Y.), and Graduate Institutes of Life Sciences and Biochemistry (Y.-J.H., G.-L.L., Y.-S.Y., C.-C.K.), National Defense Medical Center, Taipei, Taiwan; Metabolomic Research Center, China Medical University Hospital (S.-F.Y., K.K.W., C.-C.K.) and Graduate Institute of Basic Medical Science (S.-F.Y., K.K.W., C.-C.K.), China Medical University, Taichung, Taiwan; and Department of Medicine, University of Texas, Houston (K.K.W.).
Jing-Yiing WuFrom the Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (Y.-F.W., H.-F.W., G.-L.L., J.-Y.W., S.-F.Y., K.K.W., C.-C.K.); Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan (Y.-F.W.); Division of Nephrology (Y.-J.H.), Division of Infectious Diseases and Tropical Medicine (Y.-S.Y.), Department of Medicine, Tri-Service General Hospital (Y.-J.H., Y.-S.Y.), and Graduate Institutes of Life Sciences and Biochemistry (Y.-J.H., G.-L.L., Y.-S.Y., C.-C.K.), National Defense Medical Center, Taipei, Taiwan; Metabolomic Research Center, China Medical University Hospital (S.-F.Y., K.K.W., C.-C.K.) and Graduate Institute of Basic Medical Science (S.-F.Y., K.K.W., C.-C.K.), China Medical University, Taichung, Taiwan; and Department of Medicine, University of Texas, Houston (K.K.W.).
Shaw-Fang YetFrom the Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (Y.-F.W., H.-F.W., G.-L.L., J.-Y.W., S.-F.Y., K.K.W., C.-C.K.); Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan (Y.-F.W.); Division of Nephrology (Y.-J.H.), Division of Infectious Diseases and Tropical Medicine (Y.-S.Y.), Department of Medicine, Tri-Service General Hospital (Y.-J.H., Y.-S.Y.), and Graduate Institutes of Life Sciences and Biochemistry (Y.-J.H., G.-L.L., Y.-S.Y., C.-C.K.), National Defense Medical Center, Taipei, Taiwan; Metabolomic Research Center, China Medical University Hospital (S.-F.Y., K.K.W., C.-C.K.) and Graduate Institute of Basic Medical Science (S.-F.Y., K.K.W., C.-C.K.), China Medical University, Taichung, Taiwan; and Department of Medicine, University of Texas, Houston (K.K.W.).
Kenneth K WuFrom the Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (Y.-F.W., H.-F.W., G.-L.L., J.-Y.W., S.-F.Y., K.K.W., C.-C.K.); Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan (Y.-F.W.); Division of Nephrology (Y.-J.H.), Division of Infectious Diseases and Tropical Medicine (Y.-S.Y.), Department of Medicine, Tri-Service General Hospital (Y.-J.H., Y.-S.Y.), and Graduate Institutes of Life Sciences and Biochemistry (Y.-J.H., G.-L.L., Y.-S.Y., C.-C.K.), National Defense Medical Center, Taipei, Taiwan; Metabolomic Research Center, China Medical University Hospital (S.-F.Y., K.K.W., C.-C.K.) and Graduate Institute of Basic Medical Science (S.-F.Y., K.K.W., C.-C.K.), China Medical University, Taichung, Taiwan; and Department of Medicine, University of Texas, Houston (K.K.W.). kkgo@nhri.org.tw kuocc@nhri.org.tw.
Cheng-Chin KuoFrom the Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (Y.-F.W., H.-F.W., G.-L.L., J.-Y.W., S.-F.Y., K.K.W., C.-C.K.); Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan (Y.-F.W.); Division of Nephrology (Y.-J.H.), Division of Infectious Diseases and Tropical Medicine (Y.-S.Y.), Department of Medicine, Tri-Service General Hospital (Y.-J.H., Y.-S.Y.), and Graduate Institutes of Life Sciences and Biochemistry (Y.-J.H., G.-L.L., Y.-S.Y., C.-C.K.), National Defense Medical Center, Taipei, Taiwan; Metabolomic Research Center, China Medical University Hospital (S.-F.Y., K.K.W., C.-C.K.) and Graduate Institute of Basic Medical Science (S.-F.Y., K.K.W., C.-C.K.), China Medical University, Taichung, Taiwan; and Department of Medicine, University of Texas, Houston (K.K.W.). kkgo@nhri.org.tw kuocc@nhri.org.tw.
China Medical University Hospital · TWNational Tsing Hua University · TWNational Health Research Institutes · TWChina Medical University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleSystemic inflammation has emerged as a key pathophysiological process that induces multiorgan injury and causes serious human diseases. Endothelium is critical in maintaining cellular and inflammatory homeostasis, controlling systemic inflammation, and progression of inflammatory diseases. We postulated that endothelium produces and releases endogenous soluble factors to modulate inflammatory responses and protect against systemic inflammation.

objectiveTo identify endothelial cell-released soluble factors that protect against endothelial barrier dysfunction and systemic inflammation. METHODS AND

resultsWe found that conditioned medium of endothelial cells inhibited cyclooxgenase-2 and interleukin-6 expression in macrophages stimulated with lipopolysaccharide. Analysis of conditioned medium extracts by liquid chromatography-mass spectrometry showed the presence of 5-methoxytryptophan (5-MTP), but not other related tryptophan metabolites. Furthermore, endothelial cell-derived 5-MTP suppressed lipopolysaccharide-induced inflammatory responses and signaling in macrophages and endotoxemic lung tissues. Lipopolysaccharide suppressed 5-MTP level in endothelial cell-conditioned medium and reduced serum 5-MTP level in the murine sepsis model. Intraperitoneal injection of 5-MTP restored serum 5-MTP accompanied by the inhibition of lipopolysaccharide-induced endothelial leakage and suppression of lipopolysaccharide- or cecal ligation and puncture-mediated proinflammatory mediators overexpression. 5-MTP administration rescued lungs from lipopolysaccharide-induced damages and prevented sepsis-related mortality. Importantly, compared with healthy subjects, serum 5-MTP level in septic patients was decreased by 65%, indicating an important clinical relevance.

conclusionsWe conclude that 5-MTP belongs to a novel class of endothelium-derived protective molecules that defend against endothelial barrier dysfunction and excessive systemic inflammatory responses.

Indexed as

AgedAged, 80 and overAnimalsAnti-Inflammatory AgentsEndothelium, VascularEndotoxemiaFemaleHumansHuman Umbilical Vein Endothelial CellsInflammationMaleMiceMice, Inbred C57BLMiddle AgedTryptophan5-methoxytryptophanAnti-Inflammatory AgentsTryptophan5-methoxytryptophancapillary permeabilityinflammationsepsisshock

Identifiers

PMID27151398
OpenAlexW2346261156

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.