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IL-6 is constitutively expressed during lung morphogenesis and enhances fetal lung explant branching.

Abstract
Previous studies have shown that chorioamnionitis, with increased IL-6, promotes fetal lung maturation and decreases the incidence of respiratory distress syndrome in premature neonates. However, the expression pattern and the effects of IL-6 on fetal lung growth mechanisms remain unknown. IL-6 expression was assessed by in situ hybridization and by real-time PCR between 14.5 and 21.5 d postconception. Normal and nitrofen-induced hypoplastic lung explants were cultured with increasing IL-6 doses or IL-6 neutralizing antibodies. Branching, cellular proliferation (Ki-67) and MAPK phosphorylation in fetal lung explants were analyzed. Pulmonary primitive epithelium expressed IL-6 constitutively throughout all gestational ages, displaying highest levels during earliest stages. In normal and hypoplastic lung explants, IL-6 neutralizing antibodies significantly reduced, whereas IL-6 supplementation induced a biphasic effect (lower doses increased, while the highest dose did not accomplish additional effect) on branching and cellular proliferation. IL-6 enhanced p38-MAPK phosphorylation without changing MEK1/2 and JNK pathways. The present study suggests a physiological role for IL-6 on pulmonary branching mechanisms most likely involving p38-MAPK intracellular signalling pathway.
AuthorsCristina Nogueira-Silva, Marta Santos, Maria J Baptista, Rute S Moura, Jorge Correia-Pinto
JournalPediatric research (Pediatr Res) Vol. 60 Issue 5 Pg. 530-6 (Nov 2006) ISSN: 0031-3998 [Print] United States
PMID16988192 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-6
  • Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Female
  • Fetus (anatomy & histology, physiology)
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • Interleukin-6 (genetics, metabolism)
  • Lung (anatomy & histology, embryology, metabolism)
  • MAP Kinase Signaling System (physiology)
  • Mitogen-Activated Protein Kinases (metabolism)
  • Morphogenesis
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

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