Interleukin-11 inhibits adipogenesis and stimulates myelopoiesis in human long-term marrow cultures.
Interleukin-11 (IL-11) is a bone marrow (BM) stromal-derived growth factor that has been shown to stimulate murine myeloid and lymphoid cells both in vitro and in vivo and to inhibit adipogenesis in a murine fibroblast cell line. We have studied the effects of IL-11 on highly purified human BM stem and progenitor cells and on human long-term marrow cultures (LTMC). Adipocyte differentiation is an integral component of murine and human LTMC. IL-11 stimulates myeloid growth as a single cytokine when added to highly enriched CD34+, HLA-DR+ bone marrow cells. IL-11 stimulated no growth in the more primitive CD34+, HLA-DR- population even in the presence of additional cytokines. IL-11 addition to human LTMC resulted in the expansion of myeloid and mixed, but not erythroid, progenitor populations. IL-11 dramatically increased the adherent cell populations, including both stromal cells and macrophages. Treated cultures also showed marked inhibition of fat accumulation in the adherent cells due in part to a block in the differentiation of preadipocytes to adipocytes, as shown by RNA analysis using adipocyte-specific markers. These data show that IL-11 stimulates a more differentiated, although multipotential, progenitor cell in human BM and that LTMC provide a useful model for studying the effects of this cytokine in the context of the hematopoietic microenvironment.
Keller
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Herman B Wells Center for Pediatric Research, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis 46202-5225.
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Srour
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Hoffman
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Williams
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D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000187:drug effects; D002451:Cell Compartmentation / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured / Q000187:drug effects; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology
D015703:Antigens, CD; D018952:Antigens, CD34; D006684:HLA-DR Antigens; D017370:Interleukin-11