Reference - Detail
RRC ID | 41520 |
---|---|
Author | Gomi K, Kawasaki K, Kawai Y, Shiozaki M, Nishijima M. |
Title | Toll-like receptor 4-MD-2 complex mediates the signal transduction induced by flavolipin, an amino acid-containing lipid unique to Flavobacterium meningosepticum. |
Journal | J Immunol |
Abstract |
Flavolipin, an amino acid-containing lipid isolated from Flavobacterium meningosepticum, induces many immune responses. It has been shown that flavolipin does not induce an immune response of macrophages derived from C3H/HeJ mice, which possess a point mutation in Toll-like receptor 4 (TLR4). To determine whether TLR4 or the molecular complex of TLR4 and TLR4 association molecule MD-2 mediates the flavolipin signal, flavolipin responsiveness was examined by measuring NF-kappaB activation in Ba/F3 cells and Ba/F3 transfectants expressing TLR4 or both TLR4 and MD-2. Flavolipin-induced NF-kappaB activation was detected in the cells expressing both TLR4 and MD-2, but not in the other cells. Expression of CD14 in the transfectant expressing both TLR4 and MD-2 increased the sensitivity to flavolipin. Furthermore, flavolipin stereoisomers were chemically synthesized, and their abilities to induce NF-kappaB activation were examined. (R)-Flavolipin, in which the configuration of the lipid moiety is R, induced NF-kappaB activation via the TLR4-MD-2 complex, but (S)-flavolipin did not. In this study, we demonstrated the involvement of TLR4-MD-2 and CD14 in flavolipin signaling and the importance of the (R)-configuration of the flavolipin lipid moiety for the induction of an immune response via TLR4-MD-2. |
Volume | 168(6) |
Pages | 2939-43 |
Published | 2002-3-15 |
DOI | 10.4049/jimmunol.168.6.2939 |
PMID | 11884465 |
MeSH | Animals Antigens, Surface / biosynthesis Antigens, Surface / genetics Antigens, Surface / physiology* Cell Line Drosophila Proteins* Flavobacterium / immunology* Glycine / immunology Glycine / physiology* Lipids / immunology Lipids / physiology* Lipopolysaccharide Receptors / biosynthesis Lipopolysaccharide Receptors / genetics Lipoproteins / physiology* Lymphocyte Antigen 96 Macromolecular Substances Membrane Glycoproteins / biosynthesis Membrane Glycoproteins / genetics Membrane Glycoproteins / physiology* Mice NF-kappa B / metabolism Receptors, Cell Surface / biosynthesis Receptors, Cell Surface / genetics Receptors, Cell Surface / physiology* Serine / immunology Serine / physiology* Signal Transduction / immunology* Stereoisomerism Toll-Like Receptor 4 Toll-Like Receptors Transfection |
IF | 4.886 |
Times Cited | 33 |
WOS Category | IMMUNOLOGY |
Resource | |
Human and Animal Cells | Ba/F3(RCB0805) |