title: Toll-like receptor 9 regulates melanogenesis through NF-κB activation.
abstract: Toll-like receptors play essential roles in the modulation of melanogenesis, which has been implicated in the pathogenesis of hyper- or hypopigmentation-related diseases. However, little is currently known regarding the role of TLR9 in human melanocytes. TLR9 recognizes unmethylated cytosine-phosphate-guanine motif-containing oligodeoxynucleotides, and cytosine-phosphate-guanine ODN2006 acts as an hTLR9 agonist. The aim of the present study was to investigate the effect of cytosine-phosphate-guanine ODN2006 on melanogenesis in the human melanocyte cells. MTT assay and enzyme-linked immunosorbent assay indicated that ODN2006 stimulation (0, 1, 5, 10 µM) dose-dependently reduced cell viability and promoted the production of TNF-α, IL-6, and IL-8 in PIG1 melanocytes. The mRNA and protein levels of PMEL and TYRosinase were elevated at 6 h, and then decreased 24 h later, but were significantly augmented 72 h later following ODN2006 stimulation; whereas, TLR9 expressions were time-dependently increased in PIG1 melanocytes. Moreover, ultraviolet B irradiation combined with ODN2006 stimulation induced much more significant enhancement of PMEL, TYRosinase, and TLR9 mRNA and protein after three days in PIG1 melanocytes, and the similar results were obtained using the primary human melanocytes. The expression of TLR9 protein was down-regulated by TLR9 siRNA transfection. ODN2006 had an additive effect on ultraviolet B-induced melanogenesis and PMEL expression, as well as NF-κB activation, which could be blocked by TLR9 knockdown, the NF-κB specific inhibitor PDTC, or the TBK1 inhibitor BX795. Collectively, we concluded that TLR9 regulates melanogenesis through NF-κB activation, suggesting that TLR9 may play a role in microbial-induced melanogenesis.
authors.affiliation: Shaanxi Provincial Key Laboratory of Infectious and Immunological Diseases, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Nursing, Huanghuai University, Zhumadian 463000, China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Pan
authors.affiliation: Kaifeng Center for Disease Control and Prevention, Kaifeng 475004, China.
authors.forename: Yuejin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Shaanxi Provincial Key Laboratory of Infectious and Immunological Diseases, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Sun
authors.affiliation: Shaanxi Provincial Key Laboratory of Infectious and Immunological Diseases, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liang
authors.affiliation: Shaanxi Provincial Key Laboratory of Infectious and Immunological Diseases, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China Department of Translational Medicine, Institute of Integrated Medical Information, Xi'an 710016, China xiexin@nwu.edu.cn hunjun116@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
authors.affiliation: Shaanxi Provincial Key Laboratory of Infectious and Immunological Diseases, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
mesh_terms: D002470:Cell Survival; D006801:Humans; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D058951:gp100 Melanoma Antigen / Q000235:genetics / Q000378:metabolism
chemical_list: D008543:Melanins; D016328:NF-kappa B; C000615642:ODN2006; D009838:Oligodeoxyribonucleotides; C548637:PMEL protein, human; D012333:RNA, Messenger; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase
keywords: NF-κB; ODN2006; PMEL; Toll-like receptor 9; melanogenesis