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
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
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