Interleukin-10 stimulates hematopoiesis in murine osteogenic stroma.
Bone marrow from 5-fluorouracil-treated mice support osteogenesis when cultured in the presence of beta-glycerophosphate and vitamin C. These cultures are unable to support the growth of granulocyte/macrophage colony-forming units for longer than 2 weeks. In contrast, granulocyte/macrophage colony-forming units were detected for more than 6 weeks in interleukin-10 (IL-10)-treated cultures. In addition, IL-10-treated cultures contain long-term culture initiating cells, suggesting the presence of pluripotent hematopoietic cells. Apparently, IL-10 does not directly stimulate the proliferation of granulocyte/macrophage colony-forming units. Interleukin-10 is unable to stimulate [3H]-thymidine incorporation or to increase the number of granulocyte/macrophage colony-forming units in cell suspensions harvested from untreated or interleukin-10-treated bone marrow cultures. Interleukin-10 acts via an indirect pathway. Because exogenous transforming growth factor-beta (TGF-beta) reverses IL-10's stimulatory activity on myeloid progenitors, IL-10 most likely works by blocking TGF-beta synthesis, which acts as an endogenous suppressor of hematopoiesis in osteogenic marrow cultures. This is shown further by the increased numbers of granulocyte/macrophage colony-forming units in cultures treated with neutralizing anti TGF-beta antibodies (1D11.16). Interleukin-10 and 1D11.16 change the cultured bone marrow stroma from an osteogenic into a hematopoietic morphology. It may be that by blocking endogenous TGF-beta production, IL-10 drives marrow mesenchymal cells away from osteogenic differentiation toward hematopoietic support.
Van Vlasselaer
P
P
Department of Environment, Vlaamse Instelling voor Technologisch Onderzoek (VITO), Mol, Belgium.
Falla
N
N
Van Den Heuvel
R
R
Dasch
J
J
de Waal Malefijt
R
R
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010012:Osteogenesis / Q000187:drug effects; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology
D016212:Transforming Growth Factor beta; D016753:Interleukin-10