The P2X7 receptor: A main player in inflammation

Biochem Pharmacol. 2018 May:151:234-244. doi: 10.1016/j.bcp.2017.12.021. Epub 2017 Dec 27.

Abstract

Damage associated molecular patterns (DAMPs) are intracellular molecules released from infected or injured cells to activate inflammatory and reparatory responses. One of the most ancient and conserved DAMPs is extracellular ATP that exerts its phlogistic activity mainly through activation of the P2X7 receptor (P2X7R). The P2X7R is an ATP gated ion channel, expressed by most immune cells, including the monocyte-derived cell lineages, T and B lymphocytes and their precursors. Here we give an overview of recent and established literature on the role of P2X7R in septic and sterile inflammation. P2X7R ability in restraining intracellular bacteria and parasite infection by modulation of the immune response are described, with particular focus on Mycobacteria and Plasmodium. Emerging literature on the role of P2X7 in viral infections such as HIV-1 is also briefly covered. Finally, we describe the numerous intracellular pathways related to inflammation and activated by the P2X7R, including the NLRP3 inflammasome, NF-kB, NFAT, GSK3β and VEGF, and discuss the involvement of P2X7R in chronic diseases. The possible therapeutic applications of P2X7R antagonists are also described.

Keywords: ATP; Immune response; Inflammation; P2X7; Pathogens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Chronic Disease
  • Clinical Trials as Topic
  • Communicable Diseases / drug therapy
  • Communicable Diseases / immunology
  • Communicable Diseases / metabolism
  • Drug Evaluation, Preclinical
  • Humans
  • Inflammasomes / metabolism
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / immunology
  • Neurodegenerative Diseases / metabolism
  • Purinergic P2X Receptor Agonists / administration & dosage
  • Purinergic P2X Receptor Agonists / adverse effects
  • Purinergic P2X Receptor Agonists / therapeutic use*
  • Purinergic P2X Receptor Antagonists / administration & dosage
  • Purinergic P2X Receptor Antagonists / adverse effects
  • Purinergic P2X Receptor Antagonists / therapeutic use*
  • Receptors, Purinergic P2X7 / metabolism*

Substances

  • Inflammasomes
  • Purinergic P2X Receptor Agonists
  • Purinergic P2X Receptor Antagonists
  • Receptors, Purinergic P2X7