To illustrate that nerve growth factor plays a significant role in the cellular millieu of human A-549 type II alveolar epithelial cells and human fibroblasts in vitro.
Human A-549 type II alveolar epithelial cells and human fibroblasts were cultured alone and in a co-culture transwell membrane insert system with LHC-9 media. Basal nerve growth factor levels were measured for all conditions using a commercially available direct immunoassay system with a detection range of 7.8 to 500 pg/ml.
The basal levels measured in single cell culture systems was 0-20 pg/ml for both the fibroblasts and A-549 type II alveolar epithelial cells in isolated culture. Nerve growth factor levels in the co-culture system were consistently higher at 50-100 pg/ml.
Basal nerve growth factor levels are influenced by local cellular interaction between human fibroblasts and human A-549 type II alveolar epithelial cells in a co-cultured system. The levels obtained in the co-culture system are significantly higher than basal levels obtained from either cell line alone.
Nerve growth factor may serve as an important immunoregulator promoting the T-helper 2 (TH2) cell cytokine response observed in patients with asthma and idiopathic pulmonary fibrosis. Nerve growth factor may play a key role in regulating cell survival and cell death by interacting with Tyrosine kinase A and p75 neurotrophin receptors. The elevation of nerve growth factor in the co-cultured system supports the theory that there are important interactions between human fibroblasts and A-549 type II alveolar epithelial cells in vitro that influence nerve growth factor secretion. This interaction likely translates to an important in vivo relationship between alveolar and airway epithelial cells and lung fibroblasts that influences autocrine and paracrine secretion of nerve growth factor. We suggest there is a disruption in this balance that promotes surges in nerve growth factor resulting in a TH2 cell inflammatory response, fibroblast transformation, proliferation, and cell survival that contributes to the airway remodeling and fibrosis observed in patients with asthma and idiopathic pumonary fibrosis.
Susan Rohr, None.