RT Journal Article
SR Electronic
T1 Expression of GATA family of transcription factors in T-cells, monocytes and bronchial biopsies
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 466
OP 473
DO 10.1183/09031936.01.00040701
VO 18
IS 3
A1 G. Caramori
A1 S. Lim
A1 K. Ito
A1 K. Tomita
A1 T. Oates
A1 E. Jazrawi
A1 K.F. Chung
A1 P.J. Barnes
A1 I.M. Adcock
YR 2001
UL http://erj.ersjournals.com/content/18/3/466.abstract
AB GATA-binding proteins are a subfamily of zinc finger transcription factors with six members (GATA-1-6) that interact with the GATA deoxyribonucleic acid (DNA) sequence. This sequence is found in the regulatory regions of many genes including those encoding T-helper 2 (Th2)-like cytokines, receptors, adhesion molecules and enzymes, which may be important in the pathogenesis of bronchial asthma.The expression of GATA-3, -4 and -6 was investigated in peripheral blood T-lymphocytes and monocytes and bronchial biopsies from 11 normal subjects and 10 steroid-naïve asthmatic patients.Using Western blot analysis, T-cells from asthmatic subjects expressed 5 times the level of GATA-3 compared to that in normals. Confocal microscopy indicated that GATA-3 expression was both nuclear and cytoplasmic. GATA DNA binding complex containing GATA-3 was elevated in Th2 cells as determined by electrophorectic mobility shift assay. In contrast, monocytes from normal and asthmatic subjects expressed GATA-4 and -6 in equal amounts, but no GATA-3 was found. Using immunohistochemistry in bronchial biopsies, epithelial cells expressed high levels of GATA-3, GATA-4 and GATA-6 proteins. Comparison of Western blots of bronchial biopsies showed no significant differences between normal and asthmatic subjects.In conclusion, the increased expression of GATA-3 in asthmatic T-cells may underlie augmented T-helper 2-like cytokines in this disease. However, the unaltered GATA-3 expression in epithelial cells suggests a distinct role for GATA-3 in these cells unrelated to T-helper 2-like cytokine release. Finally, no evidence was found for an increased expression of GATA-4 and GATA-6 in asthma.This work was supported by Associazione per la Ricerca e la Cura dell'Asma (ARCA, Padua, Italy), Glaxo-Wellcome (UK), the Royal Brompton Hospital Clinical Research Committee and European Respiratory Society Fellowship (to G. Caramori).