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

• Autor(a) principal: Silva, Cristina Isabel Nogueira
• Data de Publicação: 2006
• Outros Autores: Santos, Marta, Baptista, Maria J., Moura, Rute S., Correia-Pinto, Jorge
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/67937
• topic: Animals; Female; Fetus; Gene Expression Regulation, Developmental; In Situ Hybridization; Interleukin-6; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Random Allocation; Rats; Rats, Sprague-Dawley; Lung; Morphogenesis; Ciências Médicas::Medicina Clínica; Science & Technology

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.