Interleukin-6 and the soluble interleukin-6 receptor induce stem cell factor and Flt-3L expression in vivo and in vitro,

Objective We recently established transgenic animals expressing either interleukin-6 (IL-6) or the soluble IL-6 receptor (sIL-6R) alone, or both components, IL-6 and the sIL-6R, in the liver. This animal model demonstrated that the expression of IL-6 in combination with its sIL-6R led to extramedullary expansion of hematopoietic progenitor cells in the spleen and liver. Materials and Methods We studied other relevant hematopoietic cytokines involved in the IL-6/sIL-6R–induced stimulation of hematopoiesis. Results Using immunohistochemistry, we showed that cell-associated stem cell factor (SCF) and Flt-3L expression were upregulated in liver and spleen only in double transgenic mice but not in IL-6 or sIL-6R single transgenic animals. Moreover, on murine NIH/3T3 fibroblasts and on human primary forskin fibroblasts, stimulation with the IL-6/sIL-6R complex, and to a lesser extent with IL-6 alone, led to induction of cellular SCF and Flt-3L expression. When human HTB-158 fibroblasts were stimulated with the IL-6/sIL-6R complex and subsequently cocultured with human umbilical cord CD34+ cells, a significant upregulation in colony growth was found. Conclusions We showed that IL-6 in combination with its soluble receptor stimulates cellular SCF and Flt-3L expression in vivo and in vitro. Cellular upregulation of SCF and Flt-3L by IL-6/sIL-6R might be used for the development of new stroma cell systems for ex vivo expansion of hematopoietic progenitor cells.