title: Autocrine Regulation of UVA-Induced IL-6 Production via Release of ATP and Activation of P2Y Receptors.
abstract: Extracellular nucleotides, such as ATP, are released from cells in response to various stimuli and act as intercellular signaling molecules through activation of P2 receptors. Exposure to the ultraviolet radiation A (UVA) component of sunlight causes molecular and cellular damage, and in this study, we investigated the involvement of extracellular nucleotides and P2 receptors in the UVA-induced cellular response. Human keratinocyte-derived HaCaT cells were irradiated with a single dose of UVA (2.5 J/cm2), and ATP release and interleukin (IL)-6 production were measured. ATP was released from cells in response to UVA irradiation, and the release was blocked by pretreatment with inhibitors of gap junction hemichannels or P2X7 receptor antagonist. IL-6 production was increased after UVA irradiation, and this increase was inhibited by ecto-nucleotidase or by antagonists of P2Y11 or P2Y13 receptor. These results suggest that UVA-induced IL-6 production is mediated by release of ATP through hemichannels and P2X7 receptor, followed by activation of P2Y11 and P2Y13 receptors. Interestingly, P2Y11 and P2Y13 were associated with the same pattern of IL-6 production, though they trigger different intracellular signaling cascades: Ca2+-dependent and PI3K-dependent, respectively. Thus, IL-6 production in response to UVA-induced ATP release involves at least two distinct pathways, mediated by activation of P2Y11 and P2Y13 receptors.
authors.affiliation: Radioisotope Research Laboratory, School of Pharmacy, Kitasato University, Shirokane, Minato-ku Tokyo, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kawano
authors.affiliation: Radioisotope Research Laboratory, School of Pharmacy, Kitasato University, Shirokane, Minato-ku Tokyo, Japan.
authors.forename: Remi
authors.initials: R
authors.lastname: Kadomatsu
authors.affiliation: Radioisotope Research Laboratory, School of Pharmacy, Kitasato University, Shirokane, Minato-ku Tokyo, Japan.
authors.forename: Miyu
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki, Noda-shi Chiba, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Kojima
authors.affiliation: Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki, Noda-shi Chiba, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Tsukimoto
authors.affiliation: Radioisotope Research Laboratory, School of Pharmacy, Kitasato University, Shirokane, Minato-ku Tokyo, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sakamoto
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D058469:Receptors, Purinergic P2X / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D015850:Interleukin-6; D058469:Receptors, Purinergic P2X; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate