Leukaemia inhibitory factor expression is inhibited by glucocorticoids through post-transcriptional mechanisms

Leukaemia inhibitory factor (LIF) is a pleiotropic cytokine which is involv ed in the regulation of the immune response and haematopoiesis, The authors investigated the regulation of the expression of LIF by glucocorticosteroi ds (GC), Endothelial cells (EC) constitutively produce LIF and this product ion is enhanced by interleukin 1 (IL-1), GC were found to inhibit the basal production of LIF by EC and to suppress its IL-l-induced augmentation, Whe ther corticosteroids suppress LIF production by blocking transcription of L IF mRNA, or by blocking LIF synthesis at a post-transcriptional level was e xamined, Northern blot hybridization analysis demonstrated that GC act main ly by decreasing the LIF mRNA level, In the presence of translation inhibit ors a superinduction of LIF mRNA was observed. Dexamethasone (DEX) at a con centration of 1 mu M was responsible for a rapid increase in the degradatio n rate of LIF mRNA which resulted in reducing its level by more than 50% wi thin 2 h, whereas the transcription rate of LIF gene was not significantly altered in these conditions. These results demonstrated that GC inhibit LIF mRNA expression mainly be increasing the turnover rate of the LIF mRNA. Th e early LIF mRNA destabilizing activity of GC was translation dependent as shown by experiments with protein translation inhibitors. The results indic ate that corticosteroids are inhibitors of LIF expression and that this inh ibition mainly occurs through post-transcriptional mechanisms. (C) 1999 Aca demic Press.