However, the most recent genome-wide asthma severity association study, conducted in more than 57 000 individuals, demonstrated significant associations for 25 loci, including three not previously associated with asthma: GATA3, MUC5AC, and KIAA1109.
However, the most recent genome-wide asthma severity association study, conducted in more than 57 000 individuals, demonstrated significant associations for 25 loci, including three not previously associated with asthma: GATA3, MUC5AC, and KIAA1109.
Moreover, IL-17A/IL-10 and RORγt/Foxp3 ratios, but not IL-4/IFN-γ or GATA-3/T-bet ratios, negatively correlated with forced expiratory volume in the first second (FEV<sub>1</sub>)/FEV<sub>1pred</sub> and Asthma Control Test Questionnaire (ACT) scores in both exacerbation group and non-exacerbation group.
Airway hyperreactivity, leukocyte infiltration, tissue remodeling, and cytokine levels as well as phosphorylated GC receptor (p-GCR), p-GATA-3, p-p38, MAPK phosphatase-1 (MKP-1), and GC-induced leucine zipper (GILZ) levels were assessed.
With the exception of CD19+ cells and IL‑12p40, M. atichisonii affected almost all factors related to asthma induction including the T helper (Th)1/Th2 transcription factors, T‑bet and GATA‑3, Th1‑related cytokines, Th2‑related cytokines and proinflammatory cytokines.
Further, low-dose LPS (1 ug) exposure was associated with increased Th1 cytokines, T-bet, Treg cytokine (IL-10, TGF-β), and Foxp3 expression, but decreased Th2 cytokines (IL-4,5,13), GATA3, Th17, and ROR-gt expression compared with the asthma group.
Furthermore, we demonstrated that the GATA3 CpG loci associated with later risk of asthma lie within a NF-κB binding site and that methylation here blocks transcription factor binding to the GATA3 promoter in the human Jurkat T-cell line.
Here, we summarize the development of a GATA-3-specific DNAzyme-a molecule class that combines the superior specificity of antisense molecules with an inherent RNA-cleaving enzymatic activity-for the treatment of type-2-driven asthma from preclinical development toward a proof-of-concept clinical study.
The results of the present study suggested that the therapeutic mechanism by which afzelin effectively treats asthma is based on reduction of Th2 cytokine via inhibition of GATA-binding protein 3 transcription factor, which is the master regulator of Th2 cytokine differentiation and production.
In this review we will try to explore the link between IL-13 and GATA3 in the progression and regulation of asthma and its possible role as a therapeutic target.
Biopsy specimens from CRS patients without asthma were subjected to immunohistochemistry for detection of T-bet and GATA-3 expression in CD3+ T cells by double labeling.
However, the percent of Th2 cells, IL-4 levels and expression of GATA-3 mRNA was markedly higher in patients with mild and moderate to severe asthma than in the control group.
GATA binding protein 3 (GATA3) is a key molecule regulating the balance in the ratio of type 1 helper T (Th1) cells to type 2 helper T (Th2) cells, which is thought to be indicative of the pathogenesis of allergic diseases such as asthma and atopic dermatitis.
Major transcription factors controlling T(H)1 and T(H)2 development, such as T-box transcription factor and GATA3, might be centrally involved in asthma and atopic diseases.
We studied the silencing of the GATA-3 gene expression using RNA interference (RNAi) delivered by a lentiviral vector, to evaluate the therapeutic role of GATA-3 short hairpin RNAs (shRNAs) in a murine model of asthma.
We report using p62-/- mice and cells that p62 acts downstream TCR activation, and is important for Th2 polarization and asthma, playing a significant role in the control of the sustained activation of NF-kappaB and late synthesis of GATA3 and IL-4 by participating in the activation of the IKK complex.
The expression level of GATA-3 may not be an essential factor to cause IL-5 hyperproduction in bronchial asthma, though GATA-3 is crucially involved in IL-5 gene transcription in human peripheral CD4+ T cells.
Interestingly, a haplotype analysis of GATA3 showed 3 related haplotypes that associated with different asthma and atopy related phenotypes among both the family and case-control data sets.
We demonstrate here that peroxisome proliferator-activated receptors (PPARs), PPAR-alpha and PPAR-gamma, which have been shown recently to be involved in the regulation of various cell types within the immune system, decrease antigen-induced airway hyperresponsiveness, lung inflammation, eosinophilia, cytokine production, and GATA-3 expression as well as serum levels of antigen-specific IgE in a murine model of human asthma.