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Impaired cortical processing of inspiratory loads in children with chronic respiratory defects
Authors:Brigitte Fauroux  Francis Renault  Pierre Yves Boelle  Christine Donzel-Raynaud  Frédéric Nicot  Annick Clément  Christian Straus  Thomas Similowski
Institution:1. Department of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, 44272-0095, Rootstown, OH, USA
2. S/M Cardiovascular Pulmonary Research, University of Colorado Health Science Center, Denver, CO, 80262, USA
Abstract:

Background

We tested the hypothesis that maternal interleukin-1β (IL-1β) pretreatment and induction of fetal cortisol synthesis activates MAP kinases and thereby affects lung fluid absorption in preterm guinea pigs.

Methods

IL-1β was administered subcutaneously daily to timed-pregnant guinea pigs for three days. Fetuses were obtained by abdominal hysterotomy and instilled with isosmolar 5% albumin into the lungs and lung fluid movement was measured over 1 h by mass balance. MAP kinase expression was measured by western blot.

Results

Lung fluid absorption was induced at 61 days (D) gestation and stimulated at 68D gestation by IL-1β. Maternal IL-1β pretreatment upregulated ERK and upstream MEK expression at both 61 and 68D gestation, albeit being much more pronounced at 61D gestation. U0126 instillation completely blocked IL-1β-induced lung fluid absorption as well as IL-1β-induced/stimulated ERK expression. Cortisol synthesis inhibition by metyrapone attenuated ERK expression and lung fluid absorption in IL-1β-pretreated fetal lungs. JNK expression after maternal IL-1β pretreatment remained unaffected at either gestation age.

Conclusion

These data implicate the ERK MAP kinase pathway as being important for IL-1β induction/stimulation of lung fluid absorption in fetal guinea pigs.
Keywords:
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