Ontogeny of toll-like receptors Tlr2 and Tlr4 in mice

Toll-like receptors (Tlr) have recently been linked to the immunostimulator y function of microbial toxins in human and mice. Tlr signals activation of nuclear factor kappaB that leads to the production of a number of proinfla mmatory mediators. Tlr4 mediates the endotoxin-induced inflammatory respons e, whereas Tlr2 may be involved in the response to yeast and Gram-positive bacterial products. To better understand age-related changes in acute infla mmatory response, we studied the ontogeny of Tlr2 and Tlr4 mRNA in murine f etal lung, liver, and placenta by quantitative reverse transcriptase-PCR, D ifferent 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 we re 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 inc reased severalfold 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.