PT  - JOURNAL ARTICLE
AU  - Rainer Zembacher
AU  - Susanna Desole
AU  - Caroline Linhart
AU  - Kathrin Watzinger
AU  - Christian M. Kähler
TI  - Proliferation of alveolar type II pneumocytes is stimulated by Jagged-1 in vitro
DP  - 2012 Sep 01
TA  - European Respiratory Journal
PG  - P3759
VI  - 40
IP  - Suppl 56
4099  - http://erj.ersjournals.com/content/40/Suppl_56/P3759.short
4100  - http://erj.ersjournals.com/content/40/Suppl_56/P3759.full
SO  - Eur Respir J2012 Sep 01; 40
AB  - Notch is an ancient cell-signaling system that regulates the specification of cell fate. Recently, Notch was found to confer antigen presenting cell function on mast cells, induce histamine release in human basophils and regulate migration and survival of eosinophils.In acute lung injury, alveolar type II cells activate macrophages, secrete soluble mediators, migrate and spread in response to the injury. Additionally, Notch stimulated myofibroblast differentiation and migration of cultured RLE-6TN cells. However, until now, nothing is known on the role of Notch activation regarding proliferation of rat alveolar type II cells.Rat alveolar type II cells (RLE 6TN) were obtained from the American Type Culture Collection (ATCC no. CRL-2300; Manassas, VA, USA) and were cultured in DMEM/Ham's F12 containing 10% fetal calf serum and L-glutamine. Cell proliferation was measured by direct cell count and the fluorometric proliferation assay EZ4U basing on tetrazolium salt reduction. Cells were incubated with the test substances in medium containing 0.5% fetal calf serum for 24h at 37°C and 5% CO2.Jagged-1 significantly stimulated proliferation of alveolar epithelial cells within a wide concentration range [5µg/ml to 100pg/ml]. The maximum effect was observed at 100ng/ml. To show specificity of the observed effect, rat alveolar type II cells were preincubated (45 min) and co-incubated with the specific gamma secretase inhibitor DAPT [10-4 M] which completely abolished the effect of Jagged-1 [ng/ml].Herewith, we report for the first time that the Jagged-1/Notch signalling pathway is affecting rat alveolar type II cell proliferation in vitro.