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DOI: 10.1055/s-2005-862731
Inflammation and ErbB Receptors in Murine Alveolar Epithelial Type II Cells
Background: Insufficient lung maturation and surfactant deficiency are major problems in preterm infants. Prenatal dexamethasone treatment as well as fetal inflammation stimulates surfactant synthesis, clinically evident as a reduction in severity of respiratory distress. ErbB receptors play a crucial regulatory role in fetal surfactant synthesis. The effects of dexamethasone and inflammation on erbB receptor expression pattern are still unclear.
Objective: We hypothesized that pre-treatment with dexamethasone, pro-inflammatory (e.g., TNF-alpha), and anti-inflammatory cytokines (e.g., IL-10) influence ligand-induced erbB receptor phosphorylation, receptor protein expression, and receptor heterodimerization in alveolar epithelial type II cells.
Design/Methods: We used MLE-12 cells, a murine type II epithelial cell line, as a model. Cells were starved at 90 % confluence in DMEM with addition of dexamethasone (10-8M), TNF-alpha (10ng/ml) or IL-10 (10ng/ml).Cells were stimulated with epidermal growth factor (EGF, 100ng/ml) or neuregulin (NRG, 33nM). Immunoprecipitation (IP) and Co-IP were done with all four erbB receptor antibodies. Blots were first probed with antiphosphotyrosine and then reprobed with the specific receptor antibodies.
Results: All four erbB receptors were present in MLE-12 cells. ErbB1 and 4 were the preferred partners for dimerization for all receptors under control conditions. Dexamethasone treatment added erbB2 receptor as a preferred dimerization partner independently of the receptor used for Co-IP. Cells treated with TNF-alpha induced erbB1/2 heterodimerization. IL-10 induced erbB4/1 dimerization and a decrease in the phosphorylation of erbB2.
Conclusions: Dexamethasone, TNF-alpha, and IL-10 changed erbB receptor dimerization patterns in fetal lung epithelial cells. Involvement of erbB1 and 2 appears to characterize a pro-inflammatory heterodimerization pattern, while erbB1 and 4 might characterize an anti-inflammatory pattern. The known synergistic effects of antenatal dexamethasone and inflammation on lung development might be regulated via a shared pathway involving erbB1 and 2. (Funded by NIH 04436A, Charles Hood Foundation, Wilhelm Hirte Stiftung, HiLF (MHH)).