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Publication : Interleukin-10 induces apoptosis in developing mast cells and macrophages.

First Author  Bailey DP Year  2006
Journal  J Leukoc Biol Volume  80
Issue  3 Pages  581-9
PubMed ID  16829633 Mgi Jnum  J:112579
Mgi Id  MGI:3662800 Doi  10.1189/jlb.0405201
Citation  Bailey DP, et al. (2006) Interleukin-10 induces apoptosis in developing mast cells and macrophages. J Leukoc Biol 80(3):581-9
abstractText  Interleukin (IL)-10 is a potent immunoregulatory cytokine capable of inhibiting the inflammatory response. As mast cells and macrophages are central effectors of inflammation, we investigated the effects of IL-10 on mast cell and macrophage development from mouse bone marrow progenitors. Bone marrow cells were cultured in IL-3 + stem cell factor (SCF), giving rise to mixed populations of mast cells and macrophages. The addition of IL-10 greatly decreased the expansion of bone marrow progenitor cells through a mechanism requiring signal tranducer and activator of transcription-3 expression. The inhibitory effects were a result of the induction of apoptosis, which occurred with caspase-3 activation and reduced mitochondrial membrane potential. Supporting a role for the mitochondrion, bone marrow cells from p53-deficient or Bcl-2 transgenic mice were partly resistant to the effects of IL-10. Further, IL-10 decreased Kit receptor expression and inhibited survival signaling by SCF or IL-3. These data indicate that IL-10 induces an intrinsic, mitochondrial apoptosis cascade in developing mast cells and macrophages through mechanisms involving blockade of growth factor receptor function. The ability of IL-10 to inhibit survival could support immune homeostasis by dampening inflammatory responses and preventing chronic inflammation.
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