1. Tryptanthrin suppresses double-stranded RNA-induced CXCL10 expression via inhibiting the phosphorylation of STAT1 in human umbilical vein endothelial cells
- Author
-
Tomoh Matsumiya, Taka Asari, Jiangli Ding, Shogo Kawaguchi, Tadaatsu Imaizumi, Hiroto Hiraga, Shinsaku Fukuda, Kazuhiko Seya, Hidezumi Kikuchi, Hirotake Sakuraba, and Noriyuki Numao
- Subjects
0301 basic medicine ,Chemokine ,Interferon-Induced Helicase, IFIH1 ,medicine.medical_treatment ,Immunology ,Umbilical vein ,03 medical and health sciences ,0302 clinical medicine ,Interferon ,medicine ,Human Umbilical Vein Endothelial Cells ,CXCL10 ,Humans ,RNA, Messenger ,Phosphorylation ,Molecular Biology ,Cells, Cultured ,RNA, Double-Stranded ,biology ,Chemistry ,virus diseases ,Interferon-beta ,Molecular biology ,Toll-Like Receptor 3 ,Chemokine CXCL10 ,030104 developmental biology ,Cytokine ,Poly I-C ,STAT1 Transcription Factor ,biology.protein ,Quinazolines ,DEAD Box Protein 58 ,Interferon Regulatory Factor-3 ,IRF3 ,030215 immunology ,Interferon regulatory factors ,medicine.drug ,Signal Transduction - Abstract
Tryptanthrin is a bioactive component of indigo plants such as Polygonum tinctrorium and known to have an anti-inflammatory activity. The aim of this study was to investigate the effects of tryptanthrin on Toll-like receptor 3 (TLR3)-mediated cytokine and chemokine expression in human umbilical vein endothelial cells (HUVEC). Herein, we found that tryptanthrin suppressed the expression of CXCL10 in HUVEC upon stimulation with a TLR3 ligand polyinosinic-polycytidylic acid (poly IC). Tryptanthrin did not inhibit poly IC-induced activation of interferon regulatory factor 3 (IRF3) or the mRNA expression of interferon (IFN)-β, while it significantly suppressed the expression of RIG-I, MDA5, and classical IFN-stimulated genes (ISGs). Tryptanthrin attenuated the phosphorylation and nuclear translocation of STAT1 in HUVEC stimulated with not only poly IC but also recombinant IFN-β. These results suggested that tryptanthrin inhibited poly IC-induced expression of CXCL10 and ISGs via suppressing the activation of STAT1 in HUVEC. Our findings indicate that tryptanthrin may be useful for regulating TLR3-mediated vascular inflammation.
- Published
- 2020