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 cytokines, including granulocyte colony-stimulating factor (G-CSF). Here, we have evaluated the mechanisms responsible for the augmentation of G-CSF gene expression by IL-17, using the murine 3T3 fibroblast cell line. Treatment of 3T3 cells, but not primary bone marrow-derived macrophages or murine monocyte/macrophage cell lines, resulted in increased steady-state G-CSF mRNA levels within 2-4 h and augmented G-CSF protein production. The combination of IL-17 and LPS enhanced G-CSF expression in an additive fashion. Stability studies revealed that IL-17 stabilized G-CSF mRNA levels, with a t1/2 of 4 h, compared to a t1/2 of less than 2 h in medium or LPS-treated cells. Induction of G-CSF expression in 3T3 cells by IL-17 did not appear to require tyrosine kinase activation or de novo protein synthesis. These studies indicate that post-transcriptional mechanisms play an important role in IL-17-induced G-CSF expression in fibroblasts and suggest that IL-17 may be useful for further delineating mechanisms of G-CSF gene regulation.
Cai
X Y
XY
Schering-Plough Research Institute, Department of Immunology, Kenilworth, NJ 07033, USA.
Gommoll
C P
CP
Justice
L
L
Narula
S K
SK
Fine
J S
JS
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D020381:Interleukin-17; D007378:Interleukins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D016207:Cytokines; D004791:Enzyme Inhibitors; D020381:Interleukin-17; D007378:Interleukins; D008070:Lipopolysaccharides; D008934:Mitogens; D011500:Protein Synthesis Inhibitors; D016179:Granulocyte Colony-Stimulating Factor; D003513:Cycloheximide; D019833:Genistein