Abbreviations: IL = interleukin; Th2 = T-helper emblem 2 Patients with allergic asthma are characterized through aberrant immune responses to environmental allergens leading to eosinophilic airway inflammation and hyperresponsiveness.


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

Patients with allergic asthma are characterized through aberrant immune responses to environmental allergens leading to eosinophilic airway inflammation and hyperresponsiveness. The activation of allergen-specific T-helper emblem 2 (Th2) lymphocytes, which breed a limited set of cytokines including interleukin (IL)-4 and IL-5, plays a crucial part in the initiation and progression of allergic asthma. commonly glucocorticoids are the most effective unsalable articles in the treatment of patients with asthma to mould the inflammatory component and hyperresponsiveness, unless they are not very selective and patients can be refractory or become insensitive to them. Novel remedy targets that modulate or inactivate disease-inducing Th2 lymphocyte may manifest to be superior and more selective. Th2 lymphocyte appear to be generated in the lung-draining lymph nodes, after which they migrate to the lung tissue.

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



A large number of known as well as unknown differentially denoteed genes were identified. A number of the known gene like as those involved in B-cell Ig production (ie, IgG-[gamma] and Ig-[epsilon] heavy chain and terminal deoxynucleotidyltransferase) and in T-cell activation (ie, signal transducer and activator of transcription 1 IL-2R, and interferon-[gamma]R) 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 small room lines, or from the same tissues after different experimental treatments or at different time points. Gene with interesting patterns of expression and/or encoding proteins of potential interest for asthma were choiceed for further functional studies. The ultimate challenge is to use this knowledge to explore of recent origin therapies for the treatment of patients with allergic asthma that are aimed at the foundation causes of the disease.

* 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 driver's seat 80082, 3508 TB Utrecht, Netherlands; e-mail:P.C.Groot@pharm.uu.nl

COPYRIGHT 2002 American society of Chest Physicians

COPYRIGHT 2002 Gale Group

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