The role of the airway epithelium in modulatory airway inflammation has been studied. It has been found that TNF-alpha and IL-1 beta are capable of stimulating gene expression of IL-6, IL-8, and G-CSF in a human bronchial epithelial cell line. Subsequent studies have demonstrated that the neuropeptide VIP is capable of inducing the production of IL-6 and IL-8. Further, the autocrine effector, Endothelin-1 is capable of inducing the production of IL-6, and IL-8, but not G-CSF or GM-CSF. Airway epithelial cells have on the cell surface, the p55 receptor for TNF-alpha, and the Type I and Type II receptors for IL-1 beta. Activators of protein kinase C, induce the solubilization and release into the medium of the TNF p55 receptor. Similarly, the IL-1 Type II receptor, which presumably does not participate in signal transduction may also be solubilized and released into the culture medium in response to cytokine stimulation. Both of these events of receptor solubilization may be a part of the epithelial response to inflammatory stimuli and may be integral to the negative control of cytokine effects on epithelial cells. This project may allow for new insight into the effect of proinflammatory cytokine on epithelial cells.
