REGULATION OF INTERLEUKIN (IL)-1-ALPHA, IL-1-BETA, 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 inter leukin (IL)-1 alpha, IL-1 beta 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 d ose-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 hormo nes on an individual cell type and develop a system in which signallin g mechanisms can be studied, we generated immortalized cell lines usin g a strategy of conditional transformation. In the cell line, TSC-936, which displayed vimentin-positive staining and morphological characte ristics of mesenchymal cells, both GH and PRL increased levels of stea dy-state mRNAs for IL-1 alpha and IL-1 beta. Nuclear run-on analysis r evealed that the transcription rate of the IL-1 beta gene was signific antly increased by GH and PRL at 30 and 60 min, respectively, but that for IL-1 alpha was not significantly changed, suggesting the possibil ity of an alternative mechanism mediating this response. These data su ggest that modulation of cytokine gene expression is one mechanism by which GH and PRL facilitate thymic development and T-cell maturation. (C) 1997 Elsevier Science Ireland Ltd.