Expression and regulation of the pattern recognition receptors Toll-like receptor-2 and Toll-like receptor-4 in the human placenta.
The placenta constitutes a physical and immunological barrier against invading infectious agents and has been suggested to be a pregnancy-specific component of the innate immune system. The aim of this study was to investigate the presence and regulation of Toll-like receptors-2 and -4 (TLR2 and TLR4) in the human placenta, because these receptors are believed to be important for immune responses against pathogens. Twenty-eight placentas from normal term pregnancies were analysed with immunohistochemistry, which showed a strong immunoreactivity for TLR2 and TLR4 in the villous and the intermediate trophoblasts. The regulation of TLR2 and TLR4 by microbial stimulus was assessed by incubating explants of term chorionic villi with zymosan or lipopolysaccharide (LPS) and analysed with real-time reverse transcriptase-polymerase chain reaction. Stimulation with zymosan and LPS readily induced interleukin (IL)-6 and IL-8 cytokine production in the placenta cultures, whereas TLR2 and TLR4 mRNA and protein expression remained at the same high level as in unstimulated explants. These data suggests a novel mechanism for the fetoplacental unit to interact with micro-organisms.
Holmlund
Ulrika
U
Department of Medicine, Karolinska Hospital and Insitutet, Stockholm, Sweden. ulrika.holmlund@ks.se
Cebers
Gvido
G
Dahlfors
Agneta R
AR
Sandstedt
Bengt
B
Bremme
Katarina
K
Ekström
Eva S
ES
Scheynius
Annika
A
D002824:Chorionic Villi / Q000276:immunology; D046508:Culture Techniques; D029721:Drosophila Proteins; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015054:Zymosan / Q000276:immunology
D029721:Drosophila Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015054:Zymosan