Increased Gilz Expression in Transgenic Mice Up-regulates Th-2 Lymphokines.
From: Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Blood
- Publish Date: Feb 2006
- ISSN: 0006-4971
- Volume: 107
- Issue: 3
- Pages: 1039-47
- Medium: Print
- Language: English
- Citation (JAMA): Cannarile Lorenza, Fallarino Francesca, Agostini Massimiliano, et al. Increased Gilz Expression in Transgenic Mice Up-regulates Th-2 Lymphokines.. Blood Feb 2006;107:1039-47
Abstract
GILZ (glucocorticoid-induced leucine zipper), a gene induced by dexamethasone, is involved in control of T lymphocyte activation and apoptosis. In the present study, using Gilz transgenic mice (TG), which overexpress GILZ in the T-cell lineage, we demonstrate that Gilz is implicated in T helper-2 (Th-2) response development. After in vitro stimulation by CD3/CD28 antibodies, peripheral naive CD4+ T cells from TG mice secrete more Th-2 cytokines such as interleukin-4 (IL-4), IL-5, IL-13, and IL-10, and produce less Th-1 cytokines such as interferon-gamma (IFN-gamma) than wild-type mice (WT). CD4+ TG lymphocytes up-regulated Th-2 cytokine expression in the specific response to ovalbumin chicken egg (OVA) antigen immunization. Up-regulation correlated with increased expression of GATA-3 and signal transducer and activator of transcription 6 (Stat6), Th-2-specific transcription factors and decreased expression of T-bet, a transcription factor involved in Th-1 differentiation. Finally, in TG mice delayed-type hypersensitivity, a Th-1 response, was inhibited and bleomycin-induced pulmonary fibrosis, a Th-2 mediated disease, was more severe. These results indicate that Gilz contributes to CD4+ commitment toward a Th-2 phenotype and suggest this contribution may be another mechanism accounting for glucocorticoid immunomodulation.
Mesh Headings (Keywords): Animals, Bleomycin, Cell Differentiation, Cytokines, Dexamethasone, GATA3 Transcription Factor, Hypersensitivity, Delayed, Immunologic Factors, Mice, Mice, Transgenic, Pulmonary Fibrosis, STAT6 Transcription Factor, Th2 Cells, Transcription Factors, Transgenes, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 16204313
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