Induction of hematopoietic cytokines from NIH 3T3 cells and bone marrow stromal cells by IL-17

IL-17 is a T cell derived cytokine, which has been shown to support hematopoiesis in vitro in the presence of a feeder layer. We have shown previously that overexpression of IL-17 using adenoviral-mediated gene transfer that IL-17 can also induce in vivo hematopoiesis in mice. initial studies in mice lacking stem cell factor (SCF) or in mice passively immunized against G-CSF suggest that these cytokines are partially responsible for IL-17 induced hematopoiesis in vivo. To investigate whether IL-17 could stimulate hematopoietic cytokines in vitro, we incubated NIH3T3 fibroblasts or primary bone marrow stromal cells from C57BL/6 mice with different doses of IL-17 for 24 hours. Cell supernatants were assayed for IL-6, II-3, and SCF. Incubation with murine IL-17 resulted in dose-dependent increases in IL-6, IL-3, and secreted SCF. Primary stromal cells had significantly greater IL-6 levels compared to NIH3T3 fibroblasts. This may be due to the fact that these cells expressed higher levels of the IL17 R when analyzed by flow cytometry. Differences in cytokine elaboration could not be accounted for by a proliferative effect of IL-17 on either 3T3 fibroblasts or primary stromal cells, as during the 24-hour incubation, there were no differences in proliferation of either cell line. These data suggest that IL-17 can act locally on stromal cells to secrete hematopoietic cytokines. Thus, we speculate that stromal cell stimulation by IL-17 is required for optimal IL-17 induced hematopoiesis.