Tryptanthrin suppresses double-stranded RNA-induced CXCL10 expression via inhibiting the phosphorylation of STAT1 in human umbilical vein endothelial cells. (January 2021)

• Record Type: Journal Article
• Authors: Kawaguchi, Shogo; Sakuraba, Hirotake; Kikuchi, Hidezumi; Numao, Noriyuki; Asari, Taka; Hiraga, Hiroto; Ding, Jiangli; Matsumiya, Tomoh; Seya, Kazuhiko; Fukuda, Shinsaku; Imaizumi, Tadaatsu
• Is Part Of: Molecular immunology. Volume 129(2021)
• Page Start: 32
• Page End: 38
• Publication Date: 2021-01
• Subjects: CXCL10 CXC chemokine ligand 10 -- dsRNA double-stranded RNA -- HUVEC human umbilical vein endothelial cell -- IFN interferon -- IFITM1 IFN-induced transmembrane protein 1 -- IL interleukin -- IRF3 interferon regulatory factor 3 -- ISG IFN-stimulated gene -- JAK Janus kinase -- LPS lipopolysaccharide -- MDA5 melanoma differentiation-associated gene 5 -- Mx1 Myxovirus resistance protein 1 -- NF-κB nuclear factor kappa B -- poly IC polyinosinic-polycytidylic acid -- RIG-I retinoic acid-inducible gene-I -- STAT signal transducers and activators of transcription -- TLR toll-like receptor; Tryptanthrin -- TLR3 -- STAT1 -- CXCL10 -- Vascular endothelial cells; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2020.11.003
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Tryptanthrin suppresses dsRNA-induced CXCL10 production in HUVEC. TLR3-mediated induction of interferon-stimulated genes is inhibited by tryptanthrin independently of IFN-β. Tryptanthrin suppresses the phosphorylation of STAT1 upon stimulation with both dsRNA and recombinant IFN-β. 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.