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FLN29, a novel interferon- and LPS-inducible gene acting as a negative regulator of toll-like receptor signaling
- Source :
- The Journal of biological chemistry. 280(50)
- Publication Year :
- 2005
-
Abstract
- Lipopolysaccharide (LPS) activates macrophages through toll-like receptor (TLR) 4. Although the mechanism of the TLR signaling pathway has been well documented, the mechanism of the negative regulation in response to LPS, particularly LPS tolerance, is still poorly understood. In this study we identified and characterized a novel interferon- and LPS-inducible gene, FLN29, which contains a TRAF6-related zinc finger motif and TRAF family member-associated NF-kappaB activator-related sequences. The induction of FLN29 was dependent on STAT1. The forced expression of FLN29 in macrophage-like RAW cells resulted in the suppression of TLR-mediated NF-kappaB and mitogen-activated protein kinase activation, while a reduced expression of FLN29 by small interfering RNA partly cancelled the down-regulation of LPS signaling. Furthermore, we demonstrated that NF-kappaB activation induced by TRAF6 and TAB2 was impaired by co-expression of FLN29, suggesting FLN29 may regulate the downstream of TRAF6. Taken together, FLN29 is a new negative feedback regulator of TLR signaling.
- Subjects :
- Lipopolysaccharides
Small interfering RNA
Time Factors
Lipopolysaccharide
Amino Acid Motifs
Regulator
Ligands
Biochemistry
chemistry.chemical_compound
Mice
Interferon
STAT1
RNA, Small Interfering
Receptor
Luciferases
Cells, Cultured
Glutathione Transferase
Oligonucleotide Array Sequence Analysis
Zinc finger
Toll-like receptor
biology
Toll-Like Receptors
Intracellular Signaling Peptides and Proteins
NF-kappa B
Zinc Fingers
Cell biology
Cytokines
medicine.drug
Plasmids
Signal Transduction
DNA, Complementary
Immunoblotting
Molecular Sequence Data
Down-Regulation
Cell Line
medicine
Escherichia coli
Animals
Humans
Amino Acid Sequence
Molecular Biology
Adaptor Proteins, Signal Transducing
TNF Receptor-Associated Factor 6
Dose-Response Relationship, Drug
Sequence Homology, Amino Acid
Macrophages
Cell Biology
Protein Structure, Tertiary
chemistry
Gene Expression Regulation
Microscopy, Fluorescence
Immunology
biology.protein
Interferons
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 280
- Issue :
- 50
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....c6dd6b41b8d06131a02e7b5cfe650a2f