RRC ID 39617
著者 Matsuguchi T, Takagi K, Musikacharoen T, Yoshikai Y.
タイトル Gene expressions of lipopolysaccharide receptors, toll-like receptors 2 and 4, are differently regulated in mouse T lymphocytes.
ジャーナル Blood
Abstract Toll-like receptors (TLRs) are a family of mammalian proteins homologous to Drosophila Toll. Human TLR2 was shown to mediate the responsiveness to lipopolysaccharide (LPS). On the other hand, gene mutations of mouse TLR4 (mTLR4) in LPS-hyporesponsive strains have suggested that mTLR4 is essential for LPS-signaling in mice, but the role of mTLR2 has not been explored. This report describes molecular cloning of the mTLR2 cDNA. Overexpression of mTLR2 and mouse CD14 conferred LPS-inducibility of c-Jun N-terminal kinase phosphorylation and nuclear factor-kappaB activation to COS7 cells, suggesting that mTLR2 is a signaling receptor for LPS. Both mTLR2 and mTLR4 genes were expressed in T cells. Treatment with anti-CD3epsilon, PMA plus ionomycin, or interleukin-2 (IL-2)/IL-15 increased mTLR2 but not mTLR4 messenger RNA (mRNA) in some T cell lines. Specific inhibitors of mitogen-activated extracellular signal-regulated kinase and fusion protein 38 (p38) kinase inhibited mTLR2 mRNA up-regulation by PMA plus ionomycin. This suggests that extracellular signal-regulated kinase and p38 kinase pathways were involved. Additionally, LPS treatment of EL-4 cell line decreased IL-4 gene expression. Our results indicate that both mTLR2 and mTLR4 are involved in LPS signaling, but their expressions are regulated differently in T cells, and that LPS may directly affect T-cell functions by binding to TLRs. (Blood. 2000;95:1378-1385)
巻・号 95(4)
ページ 1378-85
公開日 2000-2-15
PII S0006-4971(20)67087-2
PMID 10666214
MeSH Amino Acid Sequence Animals Base Sequence COS Cells Calcium-Calmodulin-Dependent Protein Kinases / metabolism Cell Line Cloning, Molecular Drosophila Proteins* Enzyme Inhibitors / pharmacology Gene Expression Regulation / drug effects Gene Expression Regulation / immunology* Humans JNK Mitogen-Activated Protein Kinases Lipopolysaccharide Receptors / genetics* Lipopolysaccharide Receptors / physiology Lipopolysaccharides / pharmacology Membrane Glycoproteins / genetics* Membrane Glycoproteins / physiology Mice Mitogen-Activated Protein Kinases / metabolism Molecular Sequence Data Organ Specificity Receptors, Cell Surface / genetics* Receptors, Cell Surface / physiology Recombinant Proteins / biosynthesis Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Spleen / immunology T-Lymphocytes / immunology* Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-Like Receptors Transcription, Genetic / immunology* Transcription, Genetic / physiology Transfection Tumor Cells, Cultured p38 Mitogen-Activated Protein Kinases
IF 17.794
引用数 131
WOS 分野 HEMATOLOGY
リソース情報
ヒト・動物細胞 CTLL-2(RCB0637)