title: ATP stimulates interleukin-6 production via P2Y receptors in human HaCaT keratinocytes.
abstract: We evaluated the role of ATP in functions of human HaCaT keratinocytes. ATP was released from HaCaT cells by changing the culture medium. Reverse transcription-polymerase chain reaction analysis revealed that HaCaT cells expressed multiple P2 purinergic receptor mRNAs. UTP was the most potent agonist to increase the intracellular Ca2+ concentration ([Ca2+]i). UTP and ATP caused the accumulation of [3H]inositol phosphates, suggesting that UTP binds to the Gq/11-coupled P2Y receptor. UTP increased IL-6 mRNA and protein levels, and the increases were inhibited by a P2 purinergic receptor antagonist (suramin, 300 microM). While a protein kinase C inhibitor (GF109203X, 10 microM) was without effect, an intracellular free Ca2+ chelator (BAPTA-AM, 50 microM) suppressed UTP-mediated IL-6 induction. These results suggest that 1) ATP is released from HaCaT cells upon physical stimulation and may act as an autocrine molecule, and 2) the stimulation of P2Y receptors causes IL-6 production via mRNA expression through [Ca2+]i elevation.
authors.affiliation: Department of Cellular Signaling, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Hirohide
authors.initials: H
authors.lastname: Yoshida
authors.forename: Daisaku
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Satoko
authors.initials: S
authors.lastname: Ohkubo
authors.forename: Norimichi
authors.initials: N
authors.lastname: Nakahata
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008301:Maleimides / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors; D014544:Uridine Triphosphate / Q000494:pharmacology
chemical_list: D007211:Indoles; D015850:Interleukin-6; D008301:Maleimides; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D003609:Dactinomycin; D004533:Egtazic Acid; D013498:Suramin; D000255:Adenosine Triphosphate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C070515:bisindolylmaleimide I; D002118:Calcium; D014544:Uridine Triphosphate