title: Localization of IL-4 and IL-4 receptors in the human term placenta, decidua and amniochorionic membranes.
abstract: There has been much recent interest in cytokine expression at the materno-fetal interface. Although T-helper 2 (Th2)-type cytokines have been described in the murine feto-placental unit, few studies have as yet been performed in human pregnancy. We have examined the production of interleukin-4 (IL-4) and expression of IL-4 receptors in the human term placenta, decidua and amniochorionic membranes. Immunohistochemical analyses revealed that cytotrophoblast, decidual macrophages and both maternal and fetal endothelial cells consistently expressed IL-4, whereas syncytiotrophoblast and placental macrophages showed an inconsistent pattern between specimens. High- and low-affinity IL-4 receptors were demonstrated by immunohistochemistry at the same cellular sites as stained for IL-4, and detection of IL-4 receptors was also variable in syncytiotrophoblast. Reverse-transcribed-polymerase chain reaction (RT-PCR) analysis showed that both IL-4 and its alternative splice variant, IL-482, are produced both in placental villi and in amniochorionic and decidual tissue. Ligand-binding assays identified the presence, on isolated term syncytiotrophoblast microvillous plasma membrane vesicle preparations, of functional high-affinity binding sites for IL-4 with a Kd in the range 102-112 pM and an apparent receptor density in the range 99-102 x 10(8) sites/mg protein. Three human choriocarcinoma (BeWo, JEG-3 and Jar) and one amnion-derived (AV3) cell lines expressed IL-4 and both high- and low-affinity IL-4 receptors. The constitutive expression of both IL-4 and IL-4 receptors, together with the novel finding of the alternative splice variant IL-482 in the immediate tissues at the materno fetal interface suggest an immunobiological role for IL-4 in human pregnancy.
authors.affiliation: Department of Pediatrics, Escola Paulista de Medicina, São Paulo, Brazil.
authors.forename: M I
authors.initials: MI
authors.lastname: de Moraes-Pinto
authors.forename: G S
authors.initials: GS
authors.lastname: Vince
authors.forename: B F
authors.initials: BF
authors.lastname: Flanagan
authors.forename: C A
authors.initials: CA
authors.lastname: Hart
authors.forename: P M
authors.initials: PM
authors.lastname: Johnson
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D002460:Cell Line; D003656:Decidua / Q000276:immunology*; D005321:Extraembryonic Membranes / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D010920:Placenta / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D019948:Receptors, Interleukin-4
chemical_list: D015703:Antigens, CD; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4