title: Quantum dots induced interferon beta expression via TRIF-dependent signaling pathways by promoting endocytosis of TLR4.
abstract: Quantum dots (QDs) are nano-sized semiconductors. Previously, intratracheal instillation of QD705s induces persistent inflammation and remodeling in the mouse lung. Expression of interferon beta (IFN-β), involved in tissue remodeling, was induced in the mouse lung. The objective of this study was to understand the mechanism of QD705 induced interferon beta (IFN-β) expression. QD705-COOH and QD705-PEG increased IFN-β and IP-10 mRNA levels during day 1 to 90 post-exposure in mouse lungs. QD705-COOH increased IFN-β expression via Toll/interleukin-1 receptor domain-containing adapter protein (TRIF) dependent Toll-like receptor (TLR) signaling pathways in macrophages RAW264.7. Silencing TRIF expression with siRNA or co-treatment with a TRIF inhibitor tremendously abolished QD705s-induced IFN-β expression. Co-treatment with a TLR4 inhibitor completely prevented IFN-β induction by QD705-COOH. QD705-COOH readily entered cells, and co-treatment with either inhibitors of endocytosis or intracellular TLRs prevented IFN-β induction. Thus, activation of the TRIF dependent TLRs pathway by promoting endocytosis of TLR4 is one of the mechanisms for immunomodulatory effects of nanoparticles.
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan, ROC.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Ho
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan, ROC.
authors.forename: Yueh-Hsia
authors.initials: YH
authors.lastname: Luo
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan, ROC.
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Chuang
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan, ROC. Electronic address: pplin@nhri.org.tw.
authors.forename: Pinpin
authors.initials: P
authors.lastname: Lin
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000819:agonists / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation; D016899:Interferon-beta / Q000819:agonists / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D045663:Quantum Dots / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D016899:Interferon-beta; D051197:Toll-Like Receptor 4; C476286:Ticam1 protein, mouse; C493487:Tlr4 protein, mouse
keywords: IFN-β; Inflammation; QD705; TLR4; TRIF