mPGES-1 and prostaglandin E2: vital role in inflammation, hypoxic response, and survival
| Autor: | Eric Herlenius, Veronica Siljehav, Per-Johan Jakobsson, Annika Olsson Hofstetter |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
musculoskeletal diseases
Male medicine.medical_specialty Time Factors Apnea Interleukin-1beta Inflammation Hyperoxia Severity of Illness Index Dinoprostone Basic Science Investigation Mice Internal medicine Respiration Medicine Animals Respiratory system Prostaglandin E2 Hypoxia Injections Intraventricular Plethysmography Whole Body Prostaglandin-E Synthases Mice Knockout business.industry Respiratory center Hypoxia (medical) Respiratory Center Intramolecular Oxidoreductases Disease Models Animal Endocrinology Mice Inbred DBA Pediatrics Perinatology and Child Health Immunology lipids (amino acids peptides and proteins) Female medicine.symptom business medicine.drug |
| Zdroj: | Pediatric Research |
| ISSN: | 1530-0447 0031-3998 |
| Popis: | Background: Apnea associated with infection and inflammation is a major medical concern in preterm infants. Prostaglandin E2 (PGE2) serves as a critical mediator between infection and apnea. We hypothesize that alteration of the microsomal PGE synthase-1 (mPGES-1) PGE2 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 PGE2 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. |
| Databáze: | OpenAIRE |
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