title: Involvement of P2Y₁₁ receptor in IFN-γ-induced IL-6 production in human keratinocytes.
abstract: Extracellular ATP and P2 receptors are reported to be involved in interleukin-6 (IL-6) production by human keratinocytes, but the role of extracellular ATP in cytokine-induced IL-6 production remains unclear. In this study, we investigated the involvement of various P2 receptors in IL-6 production induced by the Th1 cytokine interferon-gamma (IFN-γ) in a human keratinocyte cell line, HaCaT. IFN-γ increased IL-6 production in HaCaT cells. A non-selective antagonist of P2Y receptors (suramin), a selective P2Y11 receptor antagonist (NF157), ecto-nucleotidase (apyrase), and a soluble adenylate cyclase inhibitor (KH7) all inhibited IL-6 production. It was further confirmed that ATP was released from HaCaT cells stimulated with IFN-γ. These results suggest that extracellular ATP and P2Y11 receptor are involved in IFN-γ-induced IL-6 production. Knockdown of P2Y11 receptor suppressed IL-6 production, strongly supporting this idea. In conclusion, these data demonstrate that P2Y11 receptor mediates IFN-γ-induced IL-6 production in human keratinocytes, and suggest the importance of purinergic signaling in IFN-γ-induced skin inflammatory conditions, such as psoriasis.
authors: Department of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors: Makiko
authors: M
authors: Ishimaru
authors: Mitsutoshi
authors: M
authors: Tsukimoto
authors: Hitoshi
authors: H
authors: Harada
authors: Shuji
authors: S
authors: Kojima
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002460:Cell Line; D055785:Gene Knockdown Techniques; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; C109734:P2RY11 protein, human; D058919:Purinergic P2 Receptor Antagonists; D034741:RNA, Small Interfering; D018048:Receptors, Purinergic P2; D007371:Interferon-gamma; D000255:Adenosine Triphosphate