Stimulation of MAP kinase pathways after maternal IL-1beta exposure induces fetal lung fluid absorption in guinea pigs.
BACKGROUND
We tested the hypothesis that maternal interleukin-1beta (IL-1beta) pretreatment and induction of fetal cortisol synthesis activates MAP kinases and thereby affects lung fluid absorption in preterm guinea pigs.


METHODS
IL-1beta 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-1beta. Maternal IL-1beta 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-1beta-induced lung fluid absorption as well as IL-1beta-induced/stimulated ERK expression. Cortisol synthesis inhibition by metyrapone attenuated ERK expression and lung fluid absorption in IL-1beta-pretreated fetal lungs. JNK expression after maternal IL-1beta pretreatment remained unaffected at either gestation age.


CONCLUSIONS
These data implicate the ERK MAP kinase pathway as being important for IL-1beta induction/stimulation of lung fluid absorption in fetal guinea pigs.
Bhattacharjee
Reshma
R
Department of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown, OH 44272-0095, USA. bhatta.reshma@gmail.com
Li
Tianbo
T
Koshy
Shyny
S
Beard
LaMonta L
LL
Sharma
Kapil
K
Carter
Ethan P
EP
Garat
Chrystelle
C
Folkesson
Hans G
HG
D000042:Absorption / Q000187:drug effects; D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D005865:Gestational Age; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000378:metabolism*; D007279:Injections, Subcutaneous; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000196:embryology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D053583:Interleukin-1beta; D011994:Recombinant Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D006854:Hydrocortisone