Cellular FLIP long form-transgenic mice manifest a Th2 cytokine bias and enhanced allergic airway inflammation

Details

Serval ID
serval:BIB_EEA697E38943
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cellular FLIP long form-transgenic mice manifest a Th2 cytokine bias and enhanced allergic airway inflammation
Journal
Journal of Immunology
Author(s)
Wu  W., Rinaldi  L., Fortner  K. A., Russell  J. Q., Tschopp  J., Irvin  C., Budd  R. C.
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
04/2004
Volume
172
Number
8
Pages
4724-32
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Apr 15
Abstract
Cellular FLIP long form (c-FLIP(L)) is a caspase-defective homologue of caspase-8 that blocks apoptosis by death receptors. The expression of c-FLIP(L) in T cells can also augment extracellular signal-regulated kinase phosphorylation after TCR ligation via the association of c-FLIP(L) with Raf-1. This contributes to the hyperproliferative capacity of T cells from c-FLIP(L)-transgenic mice. In this study we show that activated CD4(+) T cells from c-FLIP(L)-transgenic mice produce increased amounts of Th2 cytokines and decreased amounts of Th1 cytokines. This correlates with increased serum concentrations of the Th2-dependent IgG1 and IgE. The Th2 bias of c-FLIP(L)-transgenic CD4(+) T cells parallels impaired NF-kappa B activity and increased levels of GATA-3, which contribute, respectively, to decreased IFN-gamma and increased Th2 cytokines. The Th2 bias of c-FLIP(L)-transgenic mice extends to an enhanced sensitivity to OVA-induced asthma. Taken together, these results show that c-FLIP(L) can influence cytokine gene expression to promote Th2-driven allergic reaction, in addition to its traditional role of blocking caspase activation induced by death receptors.
Keywords
Adjuvants, Immunologic/*genetics/physiology Allergens/administration & dosage/*immunology Animals CASP8 and FADD-Like Apoptosis Regulating Protein CD4-Positive T-Lymphocytes/immunology/metabolism Carrier Proteins/*genetics/physiology Cytokines/*biosynthesis DNA-Binding Proteins/biosynthesis Down-Regulation/immunology GATA3 Transcription Factor Immunoglobulin E/biosynthesis/blood Immunoglobulin G/biosynthesis/blood Interferon Type II/antagonists & inhibitors/biosynthesis Interleukin-4/biosynthesis Interphase/genetics/immunology *Intracellular Signaling Peptides and Proteins Mice Mice, Inbred C57BL Mice, Transgenic NF-kappa B/antagonists & inhibitors/metabolism Ovalbumin/administration & dosage/immunology Protein Binding/genetics/immunology Protein Isoforms/genetics/physiology Respiratory Hypersensitivity/genetics/*immunology/*pathology Th2 Cells/*immunology/*metabolism Trans-Activators/biosynthesis Transcription Factor AP-1/metabolism Up-Regulation/immunology
Pubmed
Web of science
Create date
24/01/2008 16:19
Last modification date
20/08/2019 17:16
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