Regulation and signal transduction of toll-like receptors in human chorioncarcinoma cell lines.
OBJECTIVE
Toll-like receptors (TLRs) are expressed on placental cells. The aim of this study is to analyze signaling components activated in placenta cells after TLR ligand engagement.


METHODS
In chorioncarcimoma cell lines the regulation of TLRs was determined by real time polymerase chain reaction as well as by fluorescence-activated cell sorter analysis. Activation of NF-kappaB was determined in a reporter assay system and the activation of the mitogen-activated protein kinase signaling pathways by immunoblot analysis.


RESULTS
Both lipopolysaccharide (LPS) and DNA oligonucleotides containing unmethylated CpG motifs (CpG) induced the enhanced expression of TLR2 mRNA as well as a TLR2 surface protein expression. Functionally, incubation of JAR cells with microbial stimuli such as LPS activated NF-kappaB, as well as the phosphorylation of ERK1/2 and p38 MAP kinases and secretion of interleukin-8.


CONCLUSIONS
The functional expression of TLRs on placental cells may play an important role in the initiation of an immune response in the developing fetus.
Klaffenbach
Daniela
D
Department for Pediatrics, University of Erlangen-Nürnberg, Erlangen, Germany.
Rascher
Wolfgang
W
Röllinghoff
Martin
M
Dötsch
Jörg
J
Meissner
Udo
U
Schnare
Markus
M
D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009841:Oligonucleotides / Q000494:pharmacology; D010920:Placenta / Q000166:cytology / Q000276:immunology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014327:Trophoblasts / Q000276:immunology*
D016209:Interleukin-8; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009841:Oligonucleotides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D020928:Mitogen-Activated Protein Kinases