Article Text

THE ROLE OF THE GLYCOPROTEIN 130 FAMILY OF CYTOKINES ON FETAL LUNG DEVELOPMENT MECHANISMS
  1. C Nogueira-Silva1,
  2. E Dias1,
  3. R S Moura1,
  4. J Correia-Pinto1,2
  1. 1Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal,
  2. 2Division of Pediatric Surgery, Department of Pediatrics, Hospital S Joao, Porto, Portugal

Abstract

Introduction and Aim: IL-6, IL-11, leukaemia inhibitory factor (LIF) and cardiotrophin-like cytokine (CLC) belong to the family of glycoprotein 130 (gp130)-type cytokines. These cytokines are aggregated in the same family because they all use gp130 as a signal transducer. Recently, it was demonstrated that IL-6 is expressed in fetal pulmonary epithelium and enhances lung branching. Thus, our aim was to clarify the role of IL-11, LIF and CLC during fetal lung development.

Methods: Fetal rat lungs were harvested at 13.5 days post-conception and cultured during 4 days with increasing doses of IL-11 (0, 0.01, 0.1, 1, 10, 100 ng/ml), LIF (0, 0.4, 4, 20, 40 ng/ml) and CLC (0, 0.0003, 0.003, 0.03, 0.3, 3, 30 nmol). LIF inhibition studies were also performed using neutralising antibodies. Daily pictures were made and the total number of peripheral airway buds and epithelial perimeter was determined in all lung explants. The results were expressed as day 4/day 0 ratio.

Results: A total of 226 fetal lungs were dissected. IL-11 supplementation induced no significant effect on lung growth, whereas LIF and CLC supplementation significantly decreased, in a dose-dependent way, the branching and epithelial perimeter. In addition, the inhibition of LIF action increased the measured parameters.

Conclusions: Although these cytokines share a common signal transducer, these findings suggest specific biological activities on lung development. This specificity can represent a regulatory mechanism of lung morphogenesis, intrinsic to this family, in order to achieve the correct lung growth.

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