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

• Published in: Pediatric research Vol. 60; no. 5; pp. 530 - 536
• Main Authors: Silva, Cristina Isabel Nogueira, Santos, Marta, Baptista, Maria J., Moura, Rute S., Correia-Pinto, Jorge
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Springer Nature 01-11-2006; Lippincott Williams & Wilkins
• Subjects: Animals; Biological and medical sciences; Ciências Médicas; Developmental; Female; Fetus; Fetus - anatomy & histology; Fetus - physiology; Gene Expression Regulation; Gene Expression Regulation, Developmental; General aspects; In Situ Hybridization; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lung; Lung - anatomy & histology; Lung - embryology; Lung - metabolism; MAP Kinase Signaling System; MAP Kinase Signaling System - physiology; Medical sciences; Medicina Clínica; Mitogen-Activated Protein Kinases - metabolism; Morphogenesis; Random Allocation; Rats; Rats, Sprague-Dawley; Science & Technology; Pregnancy; Interleukin 6; Morphogenesis; Branching; Pediatrics; Lung; Cytokine; Explant; Fetus; Respiratory system
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/01.pdr.0000242300.09427.3b

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.