title: Expression of intercellular adhesion molecule-1 messenger ribonucleic acid and protein in human term placental cells and its modulation by pro-inflammatory cytokines (interleukin-1beta and tumor necrosis factor alpha).
abstract: Intercellular adhesion molecule-1 (ICAM-1) is a ligand for the integrins lymphocyte function-associated antigen-1 (LFA-1) and complement receptor-3 (Mac-1), making it an important participant in many immune and inflammatory processes. Previous studies suggested that lack or reduced expression of ICAM-1 on trophoblast might partially explain its resistance to lysis by cytotoxic effectors. However, whether or not the adhesion molecule is expressed on placental cells is still a matter of debate. In this study, we determined ICAM-1 expression at mRNA, surface, and soluble protein levels on human trophoblasts throughout their functional differentiation in culture from cytotrophoblasts into syncytiotrophoblasts. Placental cells were obtained from 6 term placentas derived from normal pregnancies. ICAM-1 mRNA was detected by reverse transcription-polymerase chain reaction using two oligonucleotide primers specific for the human ICAM-1 gene. A single major DNA band of the expected size (943 base pairs) was obtained in both cytotrophoblasts and syncytiotrophoblasts. Flow cytometric analysis demonstrated expression of surface ICAM-1 protein on 45.5+/-3.5% of cytotrophoblasts. No changes were observed during differentiation in culture. Levels of the soluble form of ICAM-1 (sICAM-1) released by placental cells were undetectable when assessed by a specific ELISA. Finally, we investigated the effect of pro-inflammatory cytokines on placental ICAM-1 expression. Treatment of cultured trophoblasts for 24 h with interleukin-1beta (1 ng/ml) or tumor necrosis factor alpha (1 ng/ml) increased surface expression of ICAM-1 without inducing sICAM-1 shedding. However, on placental cells, the two cytokines exerted stimulatory effects lower than those detected on endometrial cells used as positive control. These observations document that the ICAM-1 gene is expressed in both cytotrophoblasts and syncytiotrophoblasts, suggesting that the molecule may be of value for some immune-mediated processes. On the other hand, the low sensitivity of trophoblasts to cytokine-mediated induction of ICAM-1 expression might represent a functional mechanism contributing to maternal tolerance for fetal graft.
authors.affiliation: Department of Obstetrics and Gynecology II, University of Milano, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Gaffuri
authors.forename: P
authors.initials: P
authors.lastname: Vigano
authors.forename: A
authors.initials: A
authors.lastname: Nozza
authors.forename: G
authors.initials: G
authors.lastname: Gornati
authors.forename: A M
authors.initials: AM
authors.lastname: Di Blasio
authors.forename: M
authors.initials: M
authors.lastname: Vignali
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D010920:Placenta / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase; D014327:Trophoblasts / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D012194:RNA-Directed DNA Polymerase