Regulation of interleukin (IL)-1alpha, IL-1beta, and IL-6 expression by growth hormone and prolactin in bovine thymic stromal cells.

Growth hormone (GH) and prolactin (PRL) have been implicated in T-cell development, but relatively little is known about the mechanism(s) of their actions on the multiple cell types in this complex tissue. Here, we investigated the effects of GH and PRL on the expression of interleukin (IL)-1alpha, IL-1beta and IL-6 in thymic stromal cells (TSC). These cytokine mRNAs were increased by GH, PRL and placental lactogen (PL) in primary cultures prepared from mid-gestational fetuses in a dose-dependent manner. IL-1 receptor antagonist (IL-1ra) abolished the hormone-induced IL-6 expression, suggesting that the induction of IL-6 was secondary to IL-1 activity. To examine the effects of these hormones on an individual cell type and develop a system in which signalling mechanisms can be studied, we generated immortalized cell lines using a strategy of conditional transformation. In the cell line, TSC-936, which displayed vimentin-positive staining and morphological characteristics of mesenchymal cells, both GH and PRL increased levels of steady-state mRNAs for IL-1alpha and IL-1beta. Nuclear run-on analysis revealed that the transcription rate of the IL-1beta gene was significantly increased by GH and PRL at 30 and 60 min, respectively, but that for IL-1alpha was not significantly changed, suggesting the possibility of an alternative mechanism mediating this response. These data suggest that modulation of cytokine gene expression is one mechanism by which GH and PRL facilitate thymic development and T-cell maturation.