Expression of novel cytokine transcripts in the murine placenta

It is increasingly apparent that lymphohematopoietic cytokines play a unique role during gestation. For example, placentally derived cells, including trophoblast and choriocarcinomas, respond to granulocyte-macrophage (GM)/colony-stimulating factor (CSF) and to colony-stimulating factor 1 (CSF-1), both formerly considered to be hematopoietic cytokines. It has been shown that CSF-1 is produced by the uterine epithelium and GM-CSF by the decidua. However, evidence is emerging that placentally derived cytokines may also influence reproductive function, and the question arises whether anything unique about their expression allows them to function in this particular environment. We have therefore analyzed the expression of cytokine genes in the murine placenta using a panel of cDNA probes that detect GM-CSF, CSF-1, tumor necrosis factor (TNF), interleukin (IL)-1, IL-2, IL-3, and IL-5. We report here the detection of mRNA encoding IL-1, TNF, and CSF-1 that are identical in size to those found in macrophage and fibroblast cell lines. In contrast, five distinct GM-CSF transcripts, four of which are larger than T-cell GM-CSF transcripts, were present. These novel transcripts ranged in size from 5.2, 3.9, 2.4, and 2.1 to 1 kb. Restriction analysis did not reveal any major structural alterations in the placental GM-CSF gene. Thus, the unique placental GM-CSF mRNAs detected most likely result from modified transcription of the GM-CSF gene in the placenta rather than transcription from a modified placental GM-CSF gene. Transcription of enkaryotic genes involves a number of regulatory mechanisms that can generate functionally and structurally diverse polypeptides from a single gene. Modified transcription of the GM-CSF gene in the placenta may serve to generate functionally diverse cytokines which provide the growth and differentiation signals that help to sustain pregnancy. This observation may clarify the unique role played by GM-CSF in reproductive function.