title: Roles of TLR7 in activation of NF-κB signaling of keratinocytes by imiquimod.
abstract: Imiquimod is known to exert its effects through Toll-like receptor 7 (TLR7) and/or TLR8, resulting in expression of proinflammatory cytokines and chemokines. Keratinocytes have not been reported to constitutively express TLR7 and TLR8, and the action of imiquimod is thought to be mediated by the adenine receptor, not TLR7 or TLR8. In this study, we revealed the expression of TLR7 in keratinocytes after calcium-induced differentiation. After addition of calcium to cultured keratinocytes, the immunological responses induced by imiquimod, such as activation of NF-κB and induction of TNF-α and IL-8, were more rapid and stronger. In addition, imiquimod induced the expression TLR7, and acted synergistically with calcium to induce proinflammatory cytokines. We confirmed that the responses induced by imiquimod were significantly inhibited by microRNAs suppressing TLR7 expression. These results suggest that TLR7 expressed in keratinocytes play key roles in the activation of NF-κB signaling by imiquimod, and that their modulation in keratinocytes could provide therapeutic potential for many inflammatory skin diseases.
authors.affiliation: Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Zheng Jun
authors.initials: ZJ
authors.lastname: Li
authors.forename: Kyung-Cheol
authors.initials: KC
authors.lastname: Sohn
authors.forename: Dae-Kyoung
authors.initials: DK
authors.lastname: Choi
authors.forename: Ge
authors.initials: G
authors.lastname: Shi
authors.forename: Dongkyun
authors.initials: D
authors.lastname: Hong
authors.forename: Han-Eul
authors.initials: HE
authors.lastname: Lee
authors.forename: Kyu Uang
authors.initials: KU
authors.lastname: Whang
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Myung
authors.initials: M
authors.lastname: Im
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Seo
authors.forename: Chang Deok
authors.initials: CD
authors.lastname: Kim
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D000077271:Imiquimod; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D016328:NF-kappa B; D051199:Toll-Like Receptor 7; D014409:Tumor Necrosis Factor-alpha; D000077271:Imiquimod; D002118:Calcium