Ontogeny of Toll-like receptors Tlr2 and Tlr4 in mice.
Toll-like receptors (TLR:) have recently been linked to the immunostimulatory function of microbial toxins in human and mice. TLR: signals activation of nuclear factor kappaB that leads to the production of a number of proinflammatory mediators. TLR:4 mediates the endotoxin-induced inflammatory response, whereas TLR:2 may be involved in the response to yeast and Gram-positive bacterial products. To better understand age-related changes in acute inflammatory response, we studied the ontogeny of TLR:2 and TLR:4 mRNA in murine fetal lung, liver, and placenta by quantitative reverse transcriptase-PCR. Different expression patterns were seen between the tissues and between the TLR: This is in accordance with the evidence that there are differences in the receptors for different microbial toxins and that the response is organ specific. We additionally show that the expression of TLR: was dependent on the stage of differentiation. In the liver, the levels of Tlr2 and Tlr4 were high regardless of the age. In the lung, Tlr2 and Tlr4 expression levels were barely detectable in immature fetus (d 14-15). Tlr2 and Tlr4 were increased several-fold during prenatal development and further increased after birth. The present results support the finding of a deficient inflammatory response of the immature lung to microbial toxins.
Harju
K
K
Department of Pediatrics and Biocenter Oulu, FIN-90014 University of Oulu, Oulu, Finland.
Glumoff
V
V
Hallman
M
M
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D029721:Drosophila Proteins; D005260:Female; D005315:Fetal Diseases / Q000235:genetics*; D008099:Liver / Q000196:embryology; D008171:Lung Diseases / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D012337:RNA, Ribosomal, 18S / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors
D017931:DNA Primers; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D011956:Receptors, Cell Surface; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors