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Prophylactic systemic P2X7 receptor blockade prevents experimental colitis.

Carla Caldas Marques1, Morgana T Castelo-Branco, Rodrigo G Pacheco

  • 1Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil; Laboratório de Imunologia Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil; Programa de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil.

Biochimica Et Biophysica Acta
|November 5, 2013
PubMed
Summary

Systemic blockade of the P2X7 receptor (P2X7-R) effectively prevents experimental colitis by reducing inflammation. This therapeutic strategy targets a key pathway amplifying stress and inflammation in the gut.

Keywords:
ApoptosisBrilliant blue GInnate immunityP2X7-RP2X7-R blockadeTNBS-induced colitis

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Area of Science:

  • Immunology
  • Gastroenterology
  • Pharmacology

Background:

  • The P2X7 receptor (P2X7-R) is a cation channel on immune and epithelial cells, crucial for inflammatory responses.
  • Extracellular nucleotides act as danger signals, activating P2X7-R and initiating inflammation.

Purpose of the Study:

  • To investigate the therapeutic potential of P2X7-R blockade in a rat model of inflammatory bowel disease (IBD).

Main Methods:

  • Rats with TNBS-induced colitis were treated with P2X7-R antagonists (A740003, BBG) via IP or IC injection.
  • Evaluated clinical, endoscopic, histological, and molecular markers of inflammation, including cytokine levels and immune cell infiltration.

Main Results:

  • Systemic BBG treatment significantly reduced colitis severity, myeloperoxidase activity, and collagen deposition.
  • BBG inhibited P2X7-R expression, NF-kappa B and Erk activation, and inflammatory cytokine levels (TNF-α, IL-1β).
  • Prophylactic A740003 also demonstrated protective effects against TNBS-colitis.

Conclusions:

  • Systemic P2X7-R blockade shows efficacy in preventing experimental colitis.
  • The mechanism involves a systemic anti-inflammatory action, disrupting a stress-inflammation amplification loop mediated by P2X7-R.