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Interleukin‐10 induces apoptosis in developing mast cells and macrophages
Author(s) -
Bailey Daniel P.,
Kashyap Mohit,
Bouton L. Andrew,
Murray Peter J.,
Ryan John J.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0405201
Subject(s) - biology , microbiology and biotechnology , stem cell factor , interleukin 33 , inflammation , bone marrow , progenitor cell , cytokine , apoptosis , interleukin 3 , immune system , mast cell , immunology , stem cell , interleukin , t cell , interleukin 21 , biochemistry
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 macrophge 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.