title: Bradykinin promotes migration and invasion of human immortalized trophoblasts.
abstract: Having demonstrated that the bradykinin B2 receptor (B2R) is expressed in cells that participate in trophoblast invasion in humans and guinea-pigs, we investigated the role of bradykinin (BK) on cell migration and invasion in the HTR-8/SVneo trophoblast cell line using wound healing and invasion assays. First, we documented that HTR-8/SVneo cells expressed kallikrein, B2R, B1R, MMP-2 and MMP-9 using immunocytochemistry. Incubation with BK (10.0 microMol/L) for 18 hours increased the migration index 3-fold in comparison to controls or to cells preincubated with the B2R antagonist HOE-140. BK (10.0 microMol/L) incubation yielded a similar number of proliferating and viable cells as controls, therefore the enhanced closure of the wound cannot be attributed to proliferating cells. Incubation with BK (10.0 microMol/L) for 18 hours increased the invasion index 2-fold in comparison to controls or to cells preincubated with the antagonist of the B2R. Neither the B1R ligand Lys-des-Arg9 BK, nor its antagonist Lys-(des-Arg9-Leu8), modified migration and invasion. Further support for the stimulatory effect of B2R activation on migration and invasion is provided by the 3-fold increase in the number of filopodia per cell versus controls or cells preincubated with the B2R antagonist. Bradykinin had no effect on the cellular protein content of the B2R, nor the MMP-9 and MMP-2 gelatinase activity in the culture media varied after incubation with BK. This study adds bradykinin-acting on the B2R-to the stimuli of trophoblast migration and invasion, an effect that should be integrated to other modifications of the kallikrein-kinin system in normal and pathological pregnancies.
authors: Centro de Investigaciones Médicas, Departamento de Nefrología, Escuela de Medicina Pontificia Universidad Católica, Santiago, Chile.
authors: Rafaela
authors: R
authors: Erices
authors: Jenny
authors: J
authors: Corthorn
authors: Francisco
authors: F
authors: Lisboa
authors: Gloria
authors: G
authors: Valdés
mesh_terms: D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D065169:Bradykinin B1 Receptor Antagonists; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology; D043783:Receptor, Bradykinin B1 / Q000187:drug effects; D043782:Receptor, Bradykinin B2 / Q000502:physiology; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D065169:Bradykinin B1 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C065679:icatibant; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D001920:Bradykinin