PMID- 16498264 OWN - NLM STAT- MEDLINE DCOM- 20060605 LR - 20211203 IS - 1018-2438 (Print) IS - 1018-2438 (Linking) VI - 139 IP - 4 DP - 2006 TI - Regulation of GATA-3, c-maf and T-bet mRNA expression in bronchoalveolar lavage cells and bronchial biopsies after segmental allergen challenge. PG - 306-16 AB - BACKGROUND: GATA-3 (GATA binding protein 3) and the proto-oncogene c-maf are Th2-regulating transcription factors that control the expression of interleukin (IL)-4 and IL-5, while T-bet (T-box expressed in T cells) is a Th1-specific transcription factor that controls the expression of interferon (IFN-gamma). Allergen provocation in asthmatics induces a Th2-dominated cytokine profile, but so far it is unknown whether the skewed cytokine expression is reflected by the expression of the respective transcriptional regulators. OBJECTIVE: The aim of this study was to determine the regulation of Th1- and Th2-specific transcription factors and cytokines in 10 atopic subjects with mild asthma and 5 nonatopic healthy controls at baseline and after segmental sham and allergen challenge. METHODS: The mRNA expression of GATA-3, c-maf and T-bet was determined by real-time polymerase chain reaction in bronchoalveolar lavage (BAL) cells and bronchial biopsies. The percentage of IL-4+, IL-5+ and IFN-gamma+ BAL T cells was determined by flow cytometry, and BAL levels of these cytokines were measured by ELISA. RESULTS: In BAL cells of asthmatics, the mRNA expression of all transcription factors was increased after allergen challenge. In bronchial biopsies, the basal expression of GATA-3 was increased in asthmatics compared to healthy controls but decreased after allergen challenge. Compared to sham challenge, the percentage of IL-5+/CD4+ BAL T cells was increased after allergen challenge in asthmatics while the percentage of IFN-gamma+/CD4+ and IFN-gamma+/CD8+ T cells was decreased. Expression of c-maf mRNA in BAL cells correlated with IL-4+/CD4+ BAL cells and BAL IL-5 levels. CONCLUSIONS: Segmental allergen challenge in asthmatics leads to increased GATA-3, c-maf and T-bet expression in BAL cells but not in bronchial biopsies. CI - Copyright (c) 2006 S. Karger AG, Basel. FAU - Erpenbeck, Veit J AU - Erpenbeck VJ AD - Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany. erpenbeck@item.fraunhofer.de FAU - Hagenberg, Andreas AU - Hagenberg A FAU - Krentel, Harald AU - Krentel H FAU - Discher, Marc AU - Discher M FAU - Braun, Armin AU - Braun A FAU - Hohlfeld, Jens M AU - Hohlfeld JM FAU - Krug, Norbert AU - Krug N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060222 PL - Switzerland TA - Int Arch Allergy Immunol JT - International archives of allergy and immunology JID - 9211652 RN - 0 (Allergens) RN - 0 (GATA3 Transcription Factor) RN - 0 (IL4 protein, human) RN - 0 (IL5 protein, human) RN - 0 (Interleukin-5) RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (Proto-Oncogene Proteins c-maf) RN - 0 (RNA, Messenger) RN - 0 (T-Box Domain Proteins) RN - 0 (T-box transcription factor TBX21) RN - 0 (Transcription Factors) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adolescent MH - Adult MH - Allergens/administration & dosage/*immunology MH - Asthma/*genetics/*immunology/metabolism MH - Biopsy MH - Bronchi/immunology/*metabolism MH - Bronchoalveolar Lavage Fluid/cytology MH - Female MH - GATA3 Transcription Factor/*genetics MH - *Gene Expression Regulation MH - Humans MH - Interferon-gamma/metabolism MH - Interleukin-4/metabolism MH - Interleukin-5/metabolism MH - Lymphocyte Count MH - Male MH - Proto-Oncogene Mas MH - Proto-Oncogene Proteins c-maf/*genetics MH - RNA, Messenger MH - T-Box Domain Proteins MH - T-Lymphocyte Subsets/immunology MH - Transcription Factors/*genetics EDAT- 2006/02/25 09:00 MHDA- 2006/06/06 09:00 CRDT- 2006/02/25 09:00 PHST- 2005/07/25 00:00 [received] PHST- 2005/12/20 00:00 [accepted] PHST- 2006/02/25 09:00 [pubmed] PHST- 2006/06/06 09:00 [medline] PHST- 2006/02/25 09:00 [entrez] AID - 91602 [pii] AID - 10.1159/000091602 [doi] PST - ppublish SO - Int Arch Allergy Immunol. 2006;139(4):306-16. doi: 10.1159/000091602. Epub 2006 Feb 22.