Dataset Information

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-1? (IL-1?) (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-1? 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.

Conclusion

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.

SUBMITTER: Siljehav V

PROVIDER: S-EPMC3647218 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Siljehav Veronica V Olsson Hofstetter Annika A Jakobsson Per-Johan PJ Herlenius Eric E

Pediatric research 20120827 5

<h4>Background</h4>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.<h4>Methods</h4>Nine-d-old wild-type (WT) mice, mPGES-1 heterozygote (mPGES-1(+/-)), and mPGES-1 knockout (mPGES-1(-/-)) mice were used. Respiration was i ...[more]

PMID: 22926547

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