Interleukin-1 beta stimulates interleukin-6 production in placental villous core mesenchymal cells

Abstract

Interleukin-6 (IL-6) is a pleiotropic mediator of immune function and a growth factor for a variety of hematopoietic cell types. Because IL-1 beta is known to induce IL-6 production in nonplacental mesenchymal cells and is locally produced by maternal decidua, this study was designed to determine whether IL-1 beta could regulate IL-6 production by second trimester placental villous core mesenchymal cells (VCMC) in vitro. VCMC were prepared for culture by enzymatic digestion of placentas (14-20 weeks gestation; n = 7). Immunohistochemistry performed on the confluent cells demonstrated that more than 95% of the cells had a fibroblast-like morphology and were vimentin positive, less than 5% were leukocyte common antigen (CA-45) positive, and no trophoblast contamination was demonstrated by the lack of cytokeratin staining. In dose-response experiments, a specific dose-response induction of IL-6 mRNA expression and IL-6-immunoreactive protein production by IL-1 beta was demonstrated; this was first seen at 100 pg/ml IL-1 beta [455 +/- 191 ng/ml (+/- SEM); controls, 42 +/- 16 ng/ml; P < 0.05]. In time-course studies, the addition of 10 ng/ml IL-1 beta significantly increased IL-6 production rates; this was first seen at 8 h of culture and increased in a linear fashion up to 48 h. At 48 h of culture, IL-6 levels were 17 times higher in treated VCMC (861 +/- 179 ng/ml) compared to those in nontreated VCMC (51 +/- 14 ng/ml). In summary, IL-1 beta stimulates VCMC IL-6 production in a specific dose- and time-dependent manner. From these results, we conclude that VCMC are an important source of IL-6 in second trimester placenta and that production of placental IL-6 be may regulated by decidual IL-1 beta.