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.


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.
Peters
M
M
I. Department of Medicine, Section of Pathophysiology, University of Mainz, Mainz, Germany.
Solem
F
F
Goldschmidt
J
J
Schirmacher
P
P
Rose-John
S
S
D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006411:Hematopoiesis, Extramedullary; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D007163:Immunosorbent Techniques; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000502:physiology*; D012995:Solubility; D013154:Spleen / Q000737:chemistry / Q000166:cytology; D019089:Stem Cell Factor / Q000032:analysis / Q000235:genetics*
D015850:Interleukin-6; D008565:Membrane Proteins; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D019089:Stem Cell Factor; C084881:flt3 ligand protein