Expression of toll-like receptor 4 and endotoxin responsiveness in mice during perinatal period.
Endotoxin [lipopolysaccharide (LPS)] from Gram-negative bacteria is found in amniotic fluid in intrauterine infections that associate with the risk for spontaneous premature birth, bronchopulmonary dysplasia (BPD), and respiratory distress syndrome. Toll-like receptor 4 (TLR4) is the signaling receptor for LPS. The aim was to investigate the primary inflammatory response in mice shortly after administration of LPS to the dam (14 and 17 d of pregnancy), to the newborn, or into the amniotic fluid. The expression levels of TLR4, IL-1, tumor necrosis factor-alpha, IL-6, IL-10, macrophage inflammatory protein-2, and IL-1 receptor 1 were studied with ribonuclease protection assay. In addition, TLR4 protein was analyzed with Western blotting. The fetal membranes expressed TLR4 mRNA and protein and showed an acute cytokine response to LPS when LPS was administrated into the amniotic fluid. There was distinct ontogeny in the responsiveness of fetal lung to LPS: on fetal day 14 (term 20 d), both the expression of TLR4 and the acute cytokine response were undetectable 5 h after LPS; they became detectable by fetal day 17. TLR4 and the cytokine response further increased after birth. In maternal lung, the TLR4 expression was strongest and up-regulated in parallel with the induction of the cytokines. We propose that TLR4 controls the magnitude of the LPS-induced cytokine response during the perinatal period.
Harju
Kirsi
K
Department of Pediatrics and Biocenter Oulu, University of Oulu, FIN-90014 Oulu, Finland.
Ojaniemi
Marja
M
Rounioja
Samuli
S
Glumoff
Virpi
V
Paananen
Reija
R
Vuolteenaho
Reetta
R
Hallman
Mikko
M
D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D054426:Chemokine CXCL2; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004731:Endotoxins / Q000378:metabolism*; D007249:Inflammation; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000378:metabolism; D008171:Lung Diseases / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008811:Mice, Inbred DBA; D015846:Monokines / Q000096:biosynthesis; D010920:Placenta / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis; D053573:Receptors, Interleukin-1 Type I; D012260:Ribonucleases / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
D054426:Chemokine CXCL2; D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D015846:Monokines; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D012313:RNA; D012260:Ribonucleases