ISG56 is involved in CXCL10 expression induced by TLR3 signaling in BEAS-2B bronchial epithelial cells. (2nd July 2020)

• Record Type: Journal Article
• Authors: Shiratori, Toshihiro; Imaizumi, Tadaatsu; Hirono, Koji; Kawaguchi, Shogo; Matsumiya, Tomoh; Seya, Kazuhiko; Tasaka, Sadatomo
• Is Part Of: Experimental lung research. Volume 46:Number 6(2020)
• Page Start: 195
• Page End: 202
• Publication Date: 2020-07-02
• Subjects: Bronchial epithelial cells -- CXCL10 -- IFN -- β -- ISG56 -- TLR3; Lungs -- Periodicals; Lungs -- Diseases -- Periodicals; Lung Diseases; Lung -- physiology; Respiratory System; 616.24
• DOI: 10.1080/01902148.2020.1760965
• Languages: English
• ISSNs: 0190-2148

Abstract

Abstract: Purpose and aim of the study: Bronchial epithelial cells play an important role in immune response against viral infections. Toll-like receptor 3 (TLR3) is a pathogen recognition receptor that recognizes viral double-stranded RNA (dsRNA). Activation of TLR3 induces the expression of interferon (IFN)-β, and newly synthesized IFN-β exhibits anti-viral activity by upregulating the expression of IFN-stimulated genes (ISGs). ISG56 encodes a multifunctional protein with tetratricopeptide motifs and is involved in anti-viral reactions through various mechanisms. Expression of chemokines such as CXCL10, which induces leukocyte chemotaxis, is essential for defense against airway microbes. However, regulation of chemokine expression by ISG56 in bronchial epithelial cells has not been fully investigated. The aim of this study was to examine the expression of ISG56 and its role in CXCL10 production in BEAS-2B bronchial epithelial cells treated with dsRNA. Materials and methods: BEAS-2B bronchial epithelial cells were treated with polyinosinic-polycytidylic acid (poly IC), a synthetic TLR3 ligand. The mRNA and protein expression levels of ISG 56 were analyzed by quantitative reverse transcription polymerase chain reaction and western blotting. The effect of knocking down TLR3, IFN-β, and ISG56 was examined using RNA interference. The protein expression of CXCL10 in culture medium was measured using an enzyme-linked immunosorbent assay. Results: Poly IC induced ISG56 expression in a concentration- and time- dependent manner. RNA interference showed that ISG56 induction was inhibited by knockdown of TLR3 or IFN-β and that ISG 56 knockdown decreased CXCL10 expression. Conclusions: ISG56 was induced by poly IC through TLR3/IFN-β axis, and ISG56 may positively regulated CXCL10 expression in BEAS-2B cells. ISG56 may modulate anti-viral innate immunity, at least in part, by regulating the expression of CXCL10 in bronchial epithelial cells.