Articles |

Identification of Novel Target Proteins in Th2-Dominated Allergic Inflammatory Responses Using Complementary DNA Representational Difference Analysis and Complementary DNA Microarrays* FREE TO VIEW

Peter C. Groot, PhD; B. Jerden Van Bergenhenegouwen; Frans P. Nijkamp, PhD; Antoon J. M. Van Oosterhout, PhD
Author and Funding Information

*From the Department of Pharmacology and Pathophysiology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.

Correspondence to: P. C. Groot, PhD, Department of Pharmacology and Pathophysiology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, Netherlands; e-mail:P.C.Groot@pharm.uu.nl

Chest. 2002;121(3_suppl):77S-78S. doi:10.1378/chest.121.3_suppl.77S-a
Text Size: A A A
Published online

Patients with allergic asthma are characterized by aberrant immune responses to environmental allergens leading to eosinophilic airway inflammation and hyperresponsiveness. The activation of allergen-specific T-helper type 2 (Th2) lymphocytes, which produce a limited set of cytokines including interleukin (IL)-4 and IL-5, plays a crucial role in the initiation and progression of allergic asthma. Currently, glucocorticoids are the most effective drugs in the treatment of patients with asthma to reduce the inflammatory component and hyperresponsiveness, but they are not very selective and patients can be refractory or become insensitive to them. Novel drug targets that modulate or inactivate disease-inducing Th2 lymphocytes may prove to be superior and more selective. Th2 lymphocytes appear to be generated in the lung-draining lymph nodes, after which they migrate to the lung tissue.

To identify novel potential target molecules, the expression of genes in the draining lymph node was analyzed in a mouse model of allergic asthma using representational difference analysis of complementary DNAs. In this model, immunologic and pathophysiologic features that are reminiscent of allergic asthma, such as antigen-specific IgE, airway eosinophilia and hyperresponsiveness to bronchoconstrictor stimuli, can be observed.

A large number of known as well as unknown differentially expressed genes were identified. A number of the known genes, such as those involved in B-cell Ig production (ie, IgG-γ and Ig-ε heavy chain and terminal deoxynucleotidyltransferase) and in T-cell activation (ie, signal transducer and activator of transcription 1, IL-2R, and interferon-γR) confirmed the validity of this strategy. The complementary DNA fragments thus obtained have been used to generate custom complementary DNA arrays. These arrays are hybridized with labeled RNAs from specific tissues or cell lines, or from the same tissues after different experimental treatments or at different time points. Genes with interesting patterns of expression and/or encoding proteins of potential interest for asthma were selected for further functional studies. The ultimate challenge is to use this knowledge to explore new therapies for the treatment of patients with allergic asthma that are aimed at the root causes of the disease.

Abbreviations: IL = interleukin; Th2 = T-helper type 2




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
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543