mPGES-1 and prostaglandin E2: vital role in inflammation, hypoxic response, and survival

Veronica Siljehav1, Annika Olsson Hofstetter, Per-Johan Jakobsson

  • 1Neonatal Research Unit Q2:07, Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Stockholm, Sweden.

Pediatric Research
|August 29, 2012
PubMed
Abstract

Insights

Reducing microsomal prostaglandin E synthase-1 (mPGES-1) improved survival and respiratory responses to hypoxia in mice. This suggests mPGES-1 inhibition could treat apnea and respiratory issues.

Area of Science:

  • Biomedical Research
  • Respiratory Physiology
  • Inflammation Studies

Background:

  • Apnea in preterm infants is linked to infection and inflammation.
  • Prostaglandin E2 (PGE2) mediates infection-induced apnea.
  • The role of microsomal prostaglandin E synthase-1 (mPGES-1) in respiratory control is unclear.

Purpose of the Study:

  • To investigate the influence of the mPGES-1/PGE2 pathway on respiratory control and hypoxic responses.
  • To determine if altering mPGES-1 expression affects apnea and survival.

Main Methods:

  • Respiration was measured in wild-type, mPGES-1 heterozygote, and knockout mice using flow plethysmography.
  • Mice were exposed to interleukin-1β (IL-1β) or saline, followed by normoxia, hyperoxia, and hypoxia.
  • Responses to intracerebroventricular PGE2 were also assessed.

Main Results:

  • IL-1β reduced survival in wild-type mice but not in those with reduced or absent mPGES-1.
  • Lower mPGES-1 levels prolonged gasping duration and increased gasp frequency during hypoxia.
  • PGE2 administration did not depend on mPGES-1 for its effects.

Conclusions:

  • mPGES-1 activation is crucial for responses to severe hypoxia and inflammation.
  • Reducing mPGES-1 enhances survival and autoresuscitation during hypoxia.
  • Inhibiting the mPGES-1 pathway offers a potential therapeutic strategy for apnea and respiratory disorders.

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