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Volume 2, Issue 3(Suppl) Oncol Cancer Case Rep
ISSN: 2471-8556 an open access journal
Page 49
Notes:
Cancer Therapy & Biomarkers 2016
December 05-07, 2016
conferenceseries.com
CANCER THERAPY,
BIOMARKERS & CLINICAL RESEARCH
15th World Congress on
December 05-07, 2016 Philadelphia, USA
Endothelium-derived 5-methoxytryptophan acts as a therapeutic biomarker for systemic inflammation
Cheng Chin Kuo
National Health Research Institutes, Taiwan
S ystemic inflammation has emerged as a key pathophysiological process which induces multi-organ injury and causes se-
rious human diseases. Endothelium plays a critical role in maintaining cellular and inflammatory homeostasis, 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. We found that conditioned
medium (CM) of Endothelial Cell (EC) inhibited Cyclooxgenase-2 (COX-2) and interleukin-6 expression in macrophages
stimulated with lipopolysaccharide (LPS). Analysis of CM extracts by Liquid Chromatography–Mass Spectrometry (LC-MS)
showed the presence of 5-Methoxytryptophan (5-MTP) but no other related tryptophan metabolites. Furthermore, endothelial
cells-derived 5-MTP suppressed LPS-induced inflammatory responses and signaling in macrophages and endotoxemic lung
tissues. LPS suppressed 5-MTP level in EC-CM and reduced serum 5-MTP level in the murine sepsis model. Intraperitoneal
injection of 5-MTP restored serum 5-MTP accompanied by inhibition of LPS-induced endothelial leakage and suppression of
LPS- or cecal ligation and puncture (CLP)-mediated pro-inflammatory mediators overexpression. 5-MTP administration res-
cued lungs from LPS-induced damages and prevented sepsis-related mortality. Importantly, a considerable amount of 5-MTP
was detected in healthy subjects (1.05±0.39 mM) while 5-MTP level in septic patients (0.37±0.15 mM, p<0.0001) was sig-
nificantly reduced in septic patients. We conclude that 5-MTP belongs to a novel class of endothelium-derived protective
molecules which defend against endothelial barrier dysfunction and excessive systemic inflammatory responses. Being an
endogenously produced compound, 5-MTP has the advantage of having less unexpected adverse effects. Thus, 5-MTP will be
a valuable lead compound for new inflammatory drug development. Another potential clinical application of 5-MTP is its use
as a biomarker of sepsis and other systemic inflammatory disorders. Hence, it may be useful as a “Therapeutic” biomarker for
selecting sepsis patients for 5-MTP therapy.
Biography
Cheng-Chin Kuo has completed his PhD at the age of 30 years from National Defense Medical Center, Taipei, Taiwan and postdoctoral studies from Academia
Sinica, Taipei. In 2007, he joined the National Health Research Institutes as Assistant Investigator. In 2013, he got promotion to Associate Investigator. He has
published more than 34 papers in reputed journals and has been serving as an journal reviewer. His current researches are to use comparative metabolomics
analysis coupled with cellular biochemical approaches and animal model to determine physiological relevance and pathophysiological connection between
physiological metabolites and inflammatory diseases such as systemic inflammation, vascular diseases, and cancer.
Cheng Chin Kuo, Oncol Cancer Case Rep 2016,2:3(Suppl)