Macrophage-activating lipopeptide-2 induces cyclooxygenase-2 and prostaglandin E2 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)E2 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 PGE2 by Northern blotting, RT-PCR, Western blotting and ELISA, respectively. The activation of NF-κB and MAP kinases (ERK1/2 and p38) was examined by Western blotting. The effects of inhibitors of NF-κB, MEK1/2 and p38 on MALP-2-induced PGE2 production were also evaluated. TLR2, TLR6 and TLR4 were expressed in human placental trophoblast cells. MALP-2 significantly induced COX-2 expression and enhanced PGE2 production in a dose-dependent manner. MALP-2 induced the activation of NF-κB, ERK1/2 and p38 MAPK. Inhibitors of NF-κB, MEK1/2 and p38 blocked MALP-2-inducible PGE2 production. TLR2-mediated stimulation by MALP-2 induces COX-2 and PGE2 in human placental trophoblast cells via NF-κB and MAP kinases pathways.