BPB Reports

Paper Details

BPB Reports
Vol. 4 No. 2 p.64-68 2021
Regular Article
Extracellular Adenosine Induces IL-6 Production through Activation of A2B Receptor and Epidermal Growth Factor Receptor in Human Keratinocyte HaCaT Cells
  • Mitsutoshi Tsukimoto (Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science / tsukim@rs.noda.tus.ac.jp)
Ken Watanabe 1) , Sei-ichi Tanuma 2) , Mitsutoshi Tsukimoto 1)
1) Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2) Department of Genomic Medicinal Science, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science
Received: January 12, 2021;   Accepted: March 15, 2021;   Released: March 25, 2021
Keywords: interleukin 6, adenosine, A2B receptor, epidermal growth factor receptor

Epidermal cells produce cytokines as a part of the body’s response to various external stimuli. Though extracellular ATP-induced activation of P2 receptors is involved in cytokine production in epidermal cells, it is not known whether activation of P1 receptors by extracellular adenosine leads to IL-6 production in epidermal cells. Here, we show that activation of adenosine A2B receptor induces IL-6 production via phosphorylation of epidermal growth factor receptor (EGFR) in human keratinocyte HaCaT cells. We found that treatment of HaCaT cells with 100 μM adenosine or with A2B receptor-specific agonist BAY60-6583 induced IL-6 production, and the production of IL-6 was suppressed by pretreatment with A2B receptor-specific antagonist PSB603. Adenosine- induced IL-6 production was also suppressed by A2B receptor knockdown. In addition, adenosine- and BAY60-6583-induced IL-6 production was suppressed by treatment with EGFR antagonist AG1478. Furthermore, adenosine and BAY60-6583 induced EGFR phosphorylation, and this phosphorylation was suppressed by A2B receptor knockdown. Thus, our data indicate that the A2B receptor-EGFR pathway has a role in IL-6 production. This in turn suggests that extracellular adenosine is involved in skin inflammation.