This project deals with the effect of viral infection on the function of the airway epithelial cell, the primary target of most respiratory viruses. Alterations in both epithelial-smooth interactions and epithelial ion transport will be studied. I have demonstrated that decreased epithelial neutral endopeptidase is responsible for the increased airway smooth muscle response to substance P seen with viral infections. In this project I will examine the effect of viral infections on the response to other peptide mediators, both excitatory and inhibitory and the role of decreased neutral endopeptidase in these responses. Furthermore, I will examine the role of endogenous tachykinins (whose activities are increased in the absence of neutral endopeptidase) in causing the increased parasympathetic bronchoconstriction characteristic if viral airway infection. I will also determine the effect of viral infection on the release of epithelial mediators that increase or decrease smooth muscle contraction. In studying epithelial ion transport, which regulates water secretion, I will first determine the effect of viral infection on baseline (unstimulated) sodium absorption and chloride secretion, and the dependence of such changes on epithelial prostaglandin production. I will also examine the effect of viral infection on paracellular (between cells) and transcellular (through) ion permeability. Finally, I will determine the effect of decreased epithelial neutral endopeptidase on the ion transport response to tachykinins and other peptide mediators. These studies should lead to a greater understanding of the role of viral infections in airway hypersecretion and smooth muscle hyperresponsiveness, as well as insights into the pathophysiologic mechanisms of asthma. This may ultimately provide the basis for new therapeutic strategies.
| Knobil, K; Choi, A M; Weigand, G W et al. (1998) Role of oxidants in influenza virus-induced gene expression. Am J Physiol 274:L134-42 |
| Choi, A M; Knobil, K; Otterbein, S L et al. (1996) Oxidant stress responses in influenza virus pneumonia: gene expression and transcription factor activation. Am J Physiol 271:L383-91 |
| Jacoby, D B; Choi, A M (1994) Influenza virus induces expression of antioxidant genes in human epithelial cells. Free Radic Biol Med 16:821-4 |
| Murray, T C; Jacoby, D B (1992) Viral infection increases contractile but not secretory responses to substance P in ferret trachea. J Appl Physiol 72:608-11 |
| Choi, A M; Jacoby, D B (1992) Influenza virus A infection induces interleukin-8 gene expression in human airway epithelial cells. FEBS Lett 309:327-9 |
