title: mPGES-1 and prostaglandin E2: vital role in inflammation, hypoxic response, and survival.
abstract: BACKGROUND
  Apnea associated with infection and inflammation is a major medical concern in preterm infants. Prostaglandin E(2) (PGE(2)) serves as a critical mediator between infection and apnea. We hypothesize that alteration of the microsomal PGE synthase-1 (mPGES-1) PGE(2) pathway influences respiratory control and response to hypoxia.
  
  
  METHODS
  Nine-d-old wild-type (WT) mice, mPGES-1 heterozygote (mPGES-1(+/-)), and mPGES-1 knockout (mPGES-1(-/-)) mice were used. Respiration was investigated in mice using flow plethysmography after the mice received either interleukin-1β (IL-1β) (10 µg/kg) or saline. Mice were subjected to a period of normoxia, subsequent exposure to hyperoxia, and finally either moderate (5 min) or severe hypoxia (until 1 min after last gasp).
  
  
  RESULTS
  IL-1β worsened survival in WT mice but not in mice with reduced or no mPGES-1. Reduced expression of mPGES-1 prolonged gasping duration and increased the number of gasps during hypoxia. Response to intracerebroventricular PGE(2) was not dependent on mPGES-1 expression.
  
  
  CONCLUSIONS
  Activation of mPGES-1 is involved in the rapid and vital response to severe hypoxia as well as inflammation. Attenuation of mPGES-1 appears to have no detrimental effects, yet prolongs autoresuscitation efforts and improves survival. Consequently, inhibition of the mPGES-1 pathway may serve as a potential therapeutic target for the treatment of apnea and respiratory disorders.
authors.affiliation: Neonatal Research Unit Q2:07, Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Stockholm, Sweden.
authors.forename: Veronica
authors.initials: V
authors.lastname: Siljehav
authors.forename: Annika
authors.initials: A
authors.lastname: Olsson Hofstetter
authors.forename: Per-Johan
authors.initials: PJ
authors.lastname: Jakobsson
authors.forename: Eric
authors.initials: E
authors.lastname: Herlenius
mesh_terms: D000818:Animals; D001049:Apnea / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D015232:Dinoprostone / Q000008:administration & dosage / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D018496:Hyperoxia / Q000201:enzymology / Q000503:physiopathology; D000860:Hypoxia / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D007276:Injections, Intraventricular; D053583:Interleukin-1beta; D019746:Intramolecular Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D010993:Plethysmography, Whole Body; D000071876:Prostaglandin-E Synthases; D012119:Respiration; D012125:Respiratory Center / Q000201:enzymology* / Q000503:physiopathology; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D053583:Interleukin-1beta; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone