Journal of Pharmacological Sciences (Jan 2022)

Role of neuron-derived ATP in paclitaxel-induced HMGB1 release from macrophages and peripheral neuropathy

  • Risa Domoto,
  • Fumiko Sekiguchi,
  • Riki Kamaguchi,
  • Maiko Iemura,
  • Hiroki Yamanishi,
  • Maho Tsubota,
  • Dengli Wang,
  • Masahiro Nishibori,
  • Atsufumi Kawabata

Journal volume & issue
Vol. 148, no. 1
pp. 156 – 161

Abstract

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We examined the role of ATP and high mobility group box 1 (HMGB1) in paclitaxel-induced peripheral neuropathy (PIPN). PIPN in mice was prevented by HMGB1 neutralization, macrophage depletion, and P2X7 or P2X4 blockade. Paclitaxel and ATP synergistically released HMGB1 from macrophage-like RAW264.7 cells, but not neuron-like NG108-15 cells. The paclitaxel-induced HMGB1 release from RAW264.7 cells was accelerated by co-culture with NG108-15 cells in a manner dependent on P2X7 or P2X4. Paclitaxel released ATP from NG108-15 cells, but not RAW264.7 cells. Thus, PIPN is considered to involve acceleration of HMGB1 release from macrophages through P2X7 and P2X4 activation by neuron-derived ATP.

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