Interleukin-10 induces apoptosis in developing mast cells and macrophages.
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.
Bailey
Daniel P
DP
Department of Biology, Virginia Commonwealth University, Richmond, 23284-2012, USA.
Kashyap
Mohit
M
Bouton
L Andrew
LA
Murray
Peter J
PJ
Ryan
John J
JJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology / Q000502:physiology*; D007377:Interleukin-3 / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D053078:Membrane Potential, Mitochondrial / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000276:immunology; D019089:Stem Cell Factor / Q000276:immunology
D007377:Interleukin-3; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D019089:Stem Cell Factor; D016753:Interleukin-10; D019009:Proto-Oncogene Proteins c-kit