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Increased Messenger RNA Expression of c-maf and GATA-3 After Segmental Allergen Challenge in Allergic Asthmatics* FREE TO VIEW

Veit J. Erpenbeck, MD; Jens M. Hohlfeld, MD; Marc Discher; Harald Krentel; Andreas Hagenberg; Armin Braun, PhD; Norbert Krug, MD
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*From the Fraunhofer Institute of Toxicology and Aerosol Research (Drs. Erpenbeck, Braun, and Krug), Hannover; and Department of Respiratory Medicine (Mr. Discher, Mr. Krentel, and Ms. Hagenberg), Hannover Medical School, Germany.

Correspondence to: Veit J. Erpenbeck, Nikolai-Fuchs-Strasse 1A, Hannover, Germany 30625; e-mail: erpenbeck@ita.fraunhofer.de

Chest. 2003;123(3_suppl):370S-371S. doi:10.1378/chest.123.3_suppl.370S
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Inflammation in allergic asthma is mediated by T-helper type 2 (Th2) cytokines. The expression of these cytokines is dependent on specific and nonspecific transcription factors that bind to regulatory sequences in the promoter. GATA-3 is a Th2-specific transcription factor that belongs to the zinc finger family and binds to the interleukin (IL)-5 promoter. It has also binding sites around the IL-4/IL-13 locus. Another Th2 specific transcription factor is c-maf, which transactivates the IL-4 promoter but does not appear to regulate the expression of other Th2 cytokine genes.

To investigate the regulation of these transcription factors during the formation of the allergic response, we measured the messenger RNA expression of c-maf and GATA-3 of cells obtained from BAL before and 24 h after segmental allergen and saline solution challenge of 10 subjects with mild asthma and 5 healthy control subjects. Following processing of cells, messenger RNA expression of c-maf, GATA-3, and porphobilinogen deaminase as a housekeeping gene was measured using real-time polymerase chain reaction with the Lightcycler (Roche Diagnostics; Mannheim, Germany). Relative quantification of c-maf and GATA-3 messenger RNA was performed vs the housekeeping gene porphobilinogen deaminase.

There was an increased expression of c-maf messenger RNA after segmental allergen provocation in asthmatic subjects (p < 0.01). This difference did not occur after saline solution provocation or after allergen provocation of healthy control subjects. The messenger RNA expression of GATA-3 was increased after allergen challenge when compared to baseline. The increased messenger RNA expression of c-maf and GATA-3 after allergen provocation in asthmatic subjects points to the importance of these transcriptions factors in the organization of the allergic response.

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

Supported by Deutsche Forschungsgemeinschaft (Kr1405/2-2).




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