IL-6 is constitutively expressed during lung morphogenesis and enhances fetal lung explant branching.
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.
Nogueira-Silva
Cristina
C
Fetal and Neonatal Physiology, Life and Health Sciences Research Institute (ICVS), University of Minho, 4709-057 Braga, Portugal.
Santos
Marta
M
Baptista
Maria J
MJ
Moura
Rute S
RS
Correia-Pinto
Jorge
J
D000818:Animals; D005260:Female; D005333:Fetus / Q000033:anatomy & histology* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009024:Morphogenesis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D015850:Interleukin-6; D020928:Mitogen-Activated Protein Kinases