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Preferential expression of interleukin-12 or interleukin-4 by murine bone marrow mast cells derived in mast cell
T J Smith1, L A Ducharme, J H Weis
1Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132.
In this report we demonstrate that murine bone marrow cells cultured in either interleukin (IL)-3 or mast cell growth factor (MGF, also known as c-kit ligand and stem cell factor) differentially express cytokine genes. Bone marrow cells cultured in IL-3 differentiate and proliferate, taking on a mucosal mast cell-like phenotype. These cells express the IL-4 gene. Bone marrow cells cultured in MGF take on a connective tissue mast cell-like phenotype and possess transcripts for both of the subunits of the IL-12 cytokine. Bone marrow cells cultured in both IL-3 and MGF express the IL-4 gene at lower levels than that seen for the IL-3 culture alone, but do not possess IL-12 gene transcripts. The level of IL-12 subunit transcripts derived from the MGF-derived bone marrow cells was compared to that found in splenocytes and activated macrophages, the only cells in which IL-12 production has been previously documented. Both of the IL-12 subunit transcripts were found, compared to a beta-actin control, to be present within MGF-derived cells in the same if not higher quantities than the splenocyte or macrophage cultures. Mucosal mast cells have been previously implicated in the development of the T helper type 2 (TH2) T cell phenotype via their expression of IL-4. The finding that the MGF-derived connective tissue-like mast cells possess IL-12 transcripts suggests that the development of the TH1 T cell pathway may be positively influenced by this type of mast cell.
In this report we demonstrate that murine bone marrow cells cultured in either interleukin (IL)-3 or mast cell growth factor (MGF, also known as c-kit ligand and stem cell factor) differentially express cytokine genes. Bone marrow cells cultured in IL-3 differentiate and proliferate, taking on a mucosal mast cell-like phenotype. These cells express the IL-4 gene. Bone marrow cells cultured in MGF take on a connective tissue mast cell-like phenotype and possess transcripts for both of the subunits of the IL-12 cytokine. Bone marrow cells cultured in both IL-3 and MGF express the IL-4 gene at lower levels than that seen for the IL-3 culture alone, but do not possess IL-12 gene transcripts. The level of IL-12 subunit transcripts derived from the MGF-derived bone marrow cells was compared to that found in splenocytes and activated macrophages, the only cells in which IL-12 production has been previously documented. Both of the IL-12 subunit transcripts were found, compared to a beta-actin control, to be present within MGF-derived cells in the same if not higher quantities than the splenocyte or macrophage cultures. Mucosal mast cells have been previously implicated in the development of the T helper type 2 (TH2) T cell phenotype via their expression of IL-4. The finding that the MGF-derived connective tissue-like mast cells possess IL-12 transcripts suggests that the development of the TH1 T cell pathway may be positively influenced by this type of mast cell.