Differential mRNA Expression and Production of Interleukin‐6 in Placental Trophoblast and Villous Core Compartments

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Abstract
Interleukin-6 (IL-6) is a pleiotropic protein that functions as an immunoregulatory peptide, growth factor, and endocrine hormone. IL-6 has been shown to be produced in whole placental tissue and isolated trophoblast (TC). In addition, the villous core (VC) compartment of the placenta contains cell types (fibroblasts, macrophages) capable of IL-6 production. Consequently, the present study was designed to determine the relative contribution of the TC and VC compartments to placental IL-6 production. The VC and TC compartments from term pregnancies were separated using CR-Dispase digestion and Percoll density gradient centrifugation. The VC, TC, and whole placental tissues were cultured in Dulbecco's modified Eagle's medium over a 28-h period. Relative IL-6 mRNA expression was determined by dot blot analysis and secreted IL-6 protein was determined by enzyme-linked immunosorbent assays. All three tissues demonstrated linear production of IL-6 protein over the culture period. At 28 h, whole placental tissue produced the most IL-6 (5.1 ng +/- 0.8 ng/microgram/protein) followed by TC (4.0 ng +/- 1.3 ng/micrograms) and VC (0.55 ng +/- 0.24 ng/microgram). Although production rates of IL-6 were 8.4-fold higher in TC compared to VC (P < .05), steady-state IL-6 mRNA expression was 3.5-fold higher in freshly isolated VC compared to TC (P < .0001) and 13-fold higher in VC compared to TC (P < .01) after 24 h in culture. These results demonstrate that: (1) the placenta can produce large quantities of immunoreactive IL-6 in vitro, (2) TC produce significantly more IL-6 than VC although both compartments contribute to placental IL-6 production, (3) placental IL-6 production and secretion are probably posttranscriptionally regulated since steady-state IL-6 mRNA expression in VC and TC compartments did not correlate with IL-6 production.