Toll-like receptor 4 expression levels determine the degree of LPS-susceptibility in mice.
C57BL/10ScCr (Cr) mice carry a deletion of the Toll-like receptor 4 (tlr4) gene (i.e. they are tlr4(0/0)) and are thus refractory to LPS effects. Insertion of wild-type tlr4 transgene into the tlr4(0/0) Cr germ line endowed LPS susceptibility in the two transgenic lines created, indicating that TLR4 is the only limiting factor for LPS responsiveness in Cr mice. The absolute levels of tlr4 mRNA expressed by the heterozygous transgenic (tlr4(Tr/0)), wild-type C57BL/10ScSn (Sn) (tlr4(+/+)) and heterozygous F1 (Sn x Cr) (tlr4(+/0)) mice varied markedly. However, the pattern of distribution of expression in the different organs was the same in all strains. In different biological assays (B cell mitogenicity, cytokine induction and lethal toxicity) the degree of LPS response obtained in the different strains of mice correlated with the levels of tlr4 mRNA expression. In macrophages, investigation of the LPS-induced cytokine (IL-6) response revealed a linear relationship between the response and the logarithm of TLR4-MD-2 levels.
Kalis
Christoph
C
Max-Planck-Institut für Immunbiologie, Stübeweg 51, 79108 Freiburg, Germany.
Kanzler
Benoit
B
Lembo
Annalisa
A
Poltorak
Alexander
A
Galanos
Chris
C
Freudenberg
Marina A
MA
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D029721:Drosophila Proteins; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D051218:Lymphocyte Antigen 96; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000950:Antigens, Ly; D029721:Drosophila Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors