Death-inducing tumour necrosis factor (TNF) superfamily ligands and receptors are transcribed in human placentae, cytotrophoblasts, placental macrophages and placental cell lines

Abstract

Human placentae and two of the cell types in placentae (cytotrophoblasts and macrophages) were examined by RT-PCR for transcripts of the eight TNF superfamily ligands known to induce death of activated immune cells, tumour cells, and virus-infected cells (TNFalpha, LT alpha, LT beta, FasL, TRAIL, TWEAK, LIGHT, 4-1BBL). Transcripts for all ligands were detected in term placenta but LT alpha and 4-1BBL were not detected in first trimester placenta. Although term cytotrophoblasts contained mRNAs specific for TNF alpha, LT alpha, TWEAK, and 4-1BBL, messages encoding LT beta, FasL, TRAIL, and LIGHT were absent. In term placental macrophages, messages for all ligands except 4-1BBL were present. Transcripts for the 14 receptors to which the ligands bind, six of which contain death-domains (TNFR1, Fas, DR3, DR4, DR5, DR6), were also identified using RT-PCR. Term and first trimester placentae contained transcripts for all receptors except 4-1BB. Although term cytotrophoblasts lacked receptor mRNA encoding 4-1BB and OPG, term placental macrophages lacked DcR1 and OPG. Detection of nearly all the death-inducing TNF superfamily ligands and their receptors in human placentae implies that these powerful cytokines contribute to programmed or activated cell death in this organ.