Viruses causing asthma exacerbation target the respiratory epithelium as their host tissue, and have been shown to directly induce epithelial production of pro-inflammatory cytokine and chemokines. However, there are few direct data on the interaction between respiratory epithelium and inflammatory cells though to play key roles in the pathogenesis and maintenance of asthma, i.e. eosinophils and T lymphocytes. Preliminary data suggest the hypothesis that the respiratory epithelium modulates, via secreted chemokines, the chemotaxis and activation state of eosinophils and T lymphocytes. We further hypothesize that this epithelial modulation of inflammatory cell function is more pro-inflammatory for epithelial cells from asthmatic children, compared to non-asthmatic controls; and that this epithelial up-regulation of inflammatory cell function is intensified by infection of epithelium with pathogens known to trigger asthma exacerbations. This proposal includes (1) a clinical study to determine whether nasal inflammatory/chemokine responses to viral infection differ between asthmatic children and their non-asthmatic siblings; and (2) in vitro studies to determine whether secreted mediators from or co-culture with virus-infected nasal respiratory epithelial cells modulate T lymphocyte functions or eosinophil functions. Nasal epithelial cells for the in vitro study will be obtained from children who are subjects in the clinical study. Novel aspects of the proposed studies are the use of non-invasively obtained primary epithelial cultures from clinically-defined pediatric populations of interest, and correlation of in vitro data with related clinical parameters in the same subjects. A potential outcome is the identification of specific mediator responses or cell-cell interactions which differentiate the inflammatory response to viral infection of asthmatic and non-asthmatic children, and which might ultimately by a target for new treatment strategies in the prevention of life-threatening asthma exacerbations.
| Noah, Terry L; Tudor, Gail E; Ivins, Sally S et al. (2006) Repeated measurement of nasal lavage fluid chemokines in school-age children with asthma. Ann Allergy Asthma Immunol 96:304-10 |
| Belperio, John A; Dy, Maria; Burdick, Marie D et al. (2002) Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol 27:419-27 |
