Identification of a novel isoform of MD-2 that downregulates lipopolysaccharide signaling.
MD-2 is an association molecule of Toll-like receptor 4 and is indispensable for the recognition of lipopolysaccharide. Here we report the identification of mRNA for an alternatively spliced form of MD-2, named MD-2B, which lacks the first 54 bases of exon 3. When overexpressed with MD-2, MD-2B competitively suppressed NF-kappaB activity induced by LPS. Regardless of the truncation, however, MD-2B still bound to TLR4 as efficiently as MD-2. Flow cytometric analyses revealed that MD-2B inhibited TLR4 from being expressed on the cell surface. Our data indicate that MD-2B may compete with MD-2 for binding to TLR4 and decrease the number of TLR4/MD-2 complexes on the cell surface, resulting in the inhibition of LPS signaling.
Ohta
Shoichiro
S
Department of Immunology, Saga Medical School, 5-1-1 Nabeshima, Saga, Saga 849-8501, Japan. ohtas2@post.saga-med.ac.jp
Bahrun
Uleng
U
Tanaka
Mariko
M
Kimoto
Masao
M
D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly / Q000737:chemistry* / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051218:Lymphocyte Antigen 96; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000950:Antigens, Ly; D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D020033:Protein Isoforms