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How does smoke activate mucin transcription in lung cells?

Institution: University of California, San Francisco
Investigator(s): Carol Basbaum, Ph.D.
Award Cycle: 1998 (Cycle 7) Grant #: 7RT-0152 Award: $432,415
Subject Area: Pulmonary Disease
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Healthy human airways produce several milliliters of mucus per day. In contrast, the airways of smokers suffering from bronchitis produce several hundred. The presence of excessive mucus is deleterious in that it gives rise to airflow obstruction (i.e., blockage of the conducting airways in the lung), recurrent infection and cough. There is currently only indirect evidence that smoke leads to excessive mucus production and the mechanisms are not known. We recently observed that isolated lung cells in culture, when directly exposed to cigarette smoke, are stimulated to overproduce mucin, a glycoprotein that is the major component of mucus. This was a fortunate breakthrough since it meant that the biological pathway controlling mucin production (and thus the mucus increase associated with smoking) resides in airway lung cells and can therefore be studied in detail using cell culture models of pulmonary airways. We will perform experiments to determine the molecular mechanisms involved in the induction of mucin production by cigarette smoke in lung cells. The identification of such mechanisms will directly suggest the type of drugs that can be used to inhibit mucus overproduction and thus treat its associated symptoms of airflow obstruction, recurrent infection and cough.
Publications

Molecular cloning of the amino terminal and 5' flanking region of the human MUC 5 AC gene.
Periodical: Journal of Biological Chemistry Index Medicus:
Authors: Li, D., Gallup, M. and Basbaum, C. ART
Yr: 1998 Vol: 273 Nbr: 12 Abs: Pg: 6812-6820

Cloning of the amino terminal and 5' flanking region of the human MUC5AC mucin gene and transcriptional up-regulation by bacterial exoproducts.
Periodical: Journal of Biological Chemistry Index Medicus:
Authors: Li D, Gallup M, Basbaum C ART
Yr: 1998 Vol: 273 Nbr: 12 Abs: Pg: 6812-6820

Tobacco smoke-induced lung cell proliferation mediated by tumor necrosis factor alpha converting enzyme and amphiregulin.
Periodical: Journal of Biological Chemistry Index Medicus:
Authors: Lemjabbar H, Li D, Gallup M, Sidhu S, Drori E, Basbaum C ART
Yr: 2003 Vol: 278 Nbr: Abs: Pg: 26202-26207