Macrophage-activating lipopeptide-2 induces cyclooxygenase-2 and prostaglandin E(2) via toll-like receptor 2 in human placental trophoblast cells.
We have examined whether toll-like receptor (TLR)2-mediated stimulation by macrophage-activating lipopeptide-2 (MALP-2), originally purified from Mycoplasma fermentans, induces cyclooxygenase (COX)-2 and prostaglandin (PG)E(2) in human placental trophoblast cells. The signaling mechanism by which MALP-2 exerts its effect has also been examined. Human placental trophoblast cells isolated from term placenta were used. TLR expression in trophoblast cells was confirmed by multiplex PCR and immunocytochemistry, and examined whether MALP-2 induces COX-2 and PGE(2) by Northern blotting, RT-PCR, Western blotting and ELISA, respectively. The activation of NF-kappaB and MAP kinases (ERK1/2 and p38) was examined by Western blotting. The effects of inhibitors of NF-kappaB, MEK1/2 and p38 on MALP-2-induced PGE(2) production were also evaluated. TLR2, TLR6 and TLR4 were expressed in human placental trophoblast cells. MALP-2 significantly induced COX-2 expression and enhanced PGE(2) production in a dose-dependent manner. MALP-2 induced the activation of NF-kappaB, ERK1/2 and p38 MAPK. Inhibitors of NF-kappaB, MEK1/2 and p38 blocked MALP-2-inducible PGE(2) production. TLR2-mediated stimulation by MALP-2 induces COX-2 and PGE(2) in human placental trophoblast cells via NF-kappaB and MAP kinases pathways.
Mitsunari
Masahiro
M
Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishimachi, Yonago 683-8504, Japan.
Yoshida
Souichi
S
Shoji
Takako
T
Tsukihara
Satoru
S
Iwabe
Tomio
T
Harada
Tasuku
T
Terakawa
Naoki
N
D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D055666:Lipopeptides; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects; D016328:NF-kappa B / Q000819:agonists / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology*; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism
D055666:Lipopeptides; D008565:Membrane Proteins; D016328:NF-kappa B; D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D051195:Toll-Like Receptor 2; D014108:Tosylphenylalanyl Chloromethyl Ketone; C106335:macrophage stimulatory lipopeptide 2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D015232:Dinoprostone