Stimulation of MAP kinase pathways after maternal IL-1beta exposure induces fetal lung fluid absorption in guinea pigs.

Stimulation of MAP kinase pathways after maternal IL-1beta exposure induces fetal lung fluid absorption in guinea pigs.

Bhattacharjee Reshma; Li Tianbo; Koshy Shyny; Beard LaMonta L; Sharma Kapil; Carter Ethan P; Garat Chrystelle; Folkesson Hans G

Respiratory research

2007

2007-03

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

Absorption/drug effects; Animal/*metabolism; Animals; Body Fluids/*metabolism; Extracellular Signal-Regulated MAP Kinases/metabolism; Female; Fetus/metabolism; Gestational Age; Guinea Pigs; Hydrocortisone/*metabolism; Injections; Interleukin-1beta/administration & dosage/*pharmacology; Lung/*embryology; Mitogen-Activated Protein Kinase Kinases/metabolism; Mitogen-Activated Protein Kinases/*metabolism; Pregnancy; Rats; Recombinant Proteins/administration & dosage/pharmacology; Subcutaneous

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