title: Involvement of P2Y11 receptor in silica nanoparticles 30-induced IL-6 production by human keratinocytes.
abstract: We have previously reported that P2Y11 receptor mediates IFN-γ-induced IL-6 production in human keratinocytes, suggesting the importance of purinergic signaling in skin inflammatory diseases. In this study, the involvement of various P2 receptors in IL-6 production induced by silica nanoparticle 30 (SNP30) was examined in a human keratinocyte cell line, HaCaT. Exposure to SNP30 increased IL-6 production in the cells. Ecto-nucleotidase (apyrase), a non-selective antagonist of P2Y receptors (suramin), and a selective P2Y11 receptor antagonist (NF157) all inhibited IL-6 production. Nucleotides such as ATP and UTP themselves also significantly increased IL-6 production in the cells. It was further confirmed that ATP was released from HaCaT cells exposed to SNP30. These results support the possible role of ATP in SNP30-induced IL-6 production by HaCaT cells. In conclusion, these data demonstrate that P2Y11 receptor also mediates SNP30-induced IL-6 production in human keratinocytes, confirming that the ATP-P2Y11 purinergic signaling is a common pathway of IL-6 production leading to induction of skin inflammatory diseases.
authors.affiliation: Department of Radiation Biosciences, Tokyo University of Science (TUS), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Nagakura
authors.affiliation: Department of Radiation Biosciences, Tokyo University of Science (TUS), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Negishi
authors.affiliation: Department of Radiation Biosciences, Tokyo University of Science (TUS), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Tsukimoto
authors.affiliation: Research Institute for Science and Technology, Tokyo University of Science (TUS), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Itou
authors.affiliation: Research Institute for Science and Technology, Tokyo University of Science (TUS), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Radiation Biosciences, Tokyo University of Science (TUS), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan. Electronic address: kjma@rs.noda.tus.ac.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Kojima
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003872:Dermatitis / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007202:Indicators and Reagents; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012822:Silicon Dioxide / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007202:Indicators and Reagents; D015850:Interleukin-6; C109734:P2RY11 protein, human; D058912:Purinergic P2Y Receptor Agonists; D058921:Purinergic P2Y Receptor Antagonists; D018048:Receptors, Purinergic P2; D014409:Tumor Necrosis Factor-alpha; D012822:Silicon Dioxide; D007371:Interferon-gamma; D000255:Adenosine Triphosphate
keywords: ATP; IL-6 production; P2Y11 receptor; SNP30; Skin inflammation