Articles |

Gene Therapy of Mucus Hypersecretion in Experimental Asthma* FREE TO VIEW

Christopher Evans, PhD; Farrah Kheradmand, MD; David Corry, MD; Michael Tuvim, PhD; Charles Densmore, PhD; Clifford Waldrep, PhD; Vernon Knight, MD; Burton Dickey, MD
Author and Funding Information

*From the Baylor College of Medicine and Houston Veterans Affairs Medical Center, Houston, TX.

Correspondence to: Burton Dickey, MD, Chief, Pulmonary and Critical Care Medicine, MS 151, Houston Veterans Affairs Medical Center, 2002 Holcombe Blvd, Houston, TX 77030; e-mail: bdickey@bcm.tmc.edu

Chest. 2002;121(3_suppl):90S-91S. doi:10.1378/chest.121.3_suppl.90S
Text Size: A A A
Published online

The obstruction of small airways by mucus plays a central pathophysiologic role in most cases of fatal asthma. T helper type-2 cytokines, such as interleukin (IL)-4, IL-9, and IL-13, rapidly cause dramatic metaplasia of the murine airway epithelium from a nonsecretory ciliated phenotype to mucus-secreting goblet cells in experimental allergic asthma. Accompanying this metaplasia, we have found that the exocytic regulatory protein Munc18–2 is strongly induced in the airway epithelium and that its promoter contains GATA factor, STAT-6, glucocorticoid receptor, and CREB binding sites. Munc18 protein expression is determinative for secretory function in model organisms, such that the absence of functional Munc18 protein causes a complete failure of secretion, a partial absence of Munc18 causes a partial failure, and the overexpression of Munc18 also causes a severe secretory defect. Using optimized polyethyleneimine/DNA ratios that were administered by aerosol in an atmosphere of 5% CO2, virtually 100% of murine airway epithelial cells can be transduced with reporter genes, and approximately 50% of reporter gene activity remains present after 1 week.1 This gene delivery system is being used to alter Munc18–2 gene expression to suppress mucus secretion and to reduce airflow obstruction in murine models of experimental allergic asthma.

Abbreviation: IL = interleukin


Gautam, A, Densmore, CL, Xu, B, et al (2000) Enhanced gene expression in mouse lung after PEI-DNA aerosol delivery.Mol Ther2,63-70




Gautam, A, Densmore, CL, Xu, B, et al (2000) Enhanced gene expression in mouse lung after PEI-DNA aerosol delivery.Mol Ther2,63-70
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543