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Effects of tobacco smoke on airway bactericidal activity

Institution: University of California, Davis
Investigator(s): Yuan-Pu Di, Ph.D.
Award Cycle: 2001 (Cycle 10) Grant #: 10KT-0261 Award: $87,079
Subject Area: Pulmonary Disease
Award Type: New Investigator Awards
Abstracts

Initial Award Abstract
Environmental stresses such as microorganisms and toxic chemicals have profound effects on lung injury and pulmonary disease. Airway bacterial infection has been associated with various lung diseases such as pneumonia, cystic fibrosis, and tuberculosis. Tobacco smoke is known to induce pulmonary diseases such as emphysema and lung cancer and has effects on the host defense mechanism against pathogens, but the molecular mechanisms by which this occurs is not completely understood. The long-term goal of this proposal is to investigate the functional characteristics of a novel airway specific gene, DD4, its regulation and its potential role in health and tobacco smoke related human airway diseases. We have recently identified the DD4 gene and found its expression specifically in airway serous cells. DD4 protein is a secretory protein and can be found in clinical sputum samples. The secretion of DD4 was elevated in sputum samples obtained from patients with COPD and asthma, while it diminished dramatically in all CF sputum examined. Of potential significance, our preliminary studies revealed that DD4 has antibacterial activities against both S. aureus and P. aeruginosa. These results suggest that DD4 encodes an as-yet uncharacterized bactericidal protein, which may play a significant role against bacterial infection in airways. At the completion of this research, we expect to have determined the bactericidal potency of DD4 and the regulation of the antibacterial defense mechanism of DD4 in association with tobacco smoke.
Publications

ERK1 and ERK2 activate mucin gene transcription in response to tobacco smoke exposure in human airway epithelium.
Periodical: Molecular Biology of the Cell Index Medicus:
Authors: Di YP, Basbaum C, and Wu R ABS
Yr: 2001 Vol: 12 Nbr: Abs: Pg: 226a, 1236