TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses

Details

Serval ID
serval:BIB_E808895C55DE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses
Journal
Immunity
Author(s)
Nguyen  L. T., Duncan  G. S., Mirtsos  C., Ng  M., Speiser  D. E., Shahinian  A., Marino  M. W., Mak  T. W., Ohashi  P. S., Yeh  W. C.
ISSN
1074-7613 (Print)
Publication state
Published
Issued date
09/1999
Volume
11
Number
3
Pages
379-89
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Abstract
Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) can interact with various members of the TNF receptor family. Previously, we reported that TRAF2-deficient mice die prematurely and have elevated serum TNF levels. In this study, we demonstrate that TRAF2-deficient macrophages produce increased amounts of nitric oxide (NO) and TNF in response to TNF stimulation. Furthermore, we could enhance the survival of TRAF2-deficient mice by eliminating either TNF or TNFR1. Using these double-knockout mice, we show that in the absence of TRAF2, the T helper-dependent antibody response, CD40-mediated proliferation, and NF-kappaB activation are defective. These data demonstrate two important roles of TRAF2, one as a negative regulator of certain TNFR1 signals and the other as a positive mediator of CD40 signaling.
Keywords
Animals Antigens, CD/*metabolism Antigens, CD40/*metabolism Cell Division Cells, Cultured Female Immunoglobulin Class Switching Immunoglobulin Isotypes Interleukin-12/biosynthesis Macrophages, Peritoneal/cytology/metabolism Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout NF-kappa B/metabolism Nitric Oxide/biosynthesis Nitric Oxide Synthase/genetics Nitric Oxide Synthase Type II Phenotype Proteins/genetics/*physiology Receptors, Tumor Necrosis Factor/*metabolism Receptors, Tumor Necrosis Factor, Type I *Signal Transduction Spleen/cytology TNF Receptor-Associated Factor 2 Tumor Necrosis Factor-alpha/biosynthesis Vesicular stomatitis-Indiana virus
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:32
Last modification date
20/08/2019 16:10
Usage data