REGULATION OF GRANULOCYTE-COLONY-STIMULATING FACTOR GENE-EXPRESSION BY INTERLEUKIN-17

Interleukin-17 (IL-17) has been previously reported to induce stromal cells to produce a number of hematopoietic and proinflammatory cytokin es, including granulocyte colony-stimulating factor (G-CSF). Here, we have evaluated the mechanisms responsible for the augmentation of G-CS F gene expression by IL-17, using the murine 3T3 fibroblast cell line. Treatment of 3T3 cells, but not primary bone marrow-derived macrophag es or murine monocyte/macrophage cell lines, resulted in increased ste ady-state G-CSF mRNA levels within 2-4 h and augmented G-CSF protein p roduction. The combination of IL-17 and LPS enhanced G-CSF expression in an additive fashion. Stability studies revealed that IL-17 stabiliz ed G-CSF mRNA levels, with a t(1/2) of 4 h, compared to a t(1/2) of le ss than 2 h in medium or LPS-treated cells. Induction of G-CSF express ion in 3T3 cells by IL-17 did not appear to require tyrosine kinase ac tivation or de novo protein synthesis. These studies indicate that pos t-transcriptional mechanisms play an important role in IL-17-induced G -CSF expression in fibroblasts and suggest that IL-17 may be useful fo r further delineating mechanisms of G-CSF gene regulation. (C) 1998 El sevier Science B.V. All rights reserved.