Interleukin-10 induces apoptosis in developing mast cells and macrophages

Journal of Leukocyte Biology

Mohit Kashyap²  Daniel P. Bailey²  Peter J. Murray¹  John J. Ryan²  L. Andrew Bouton² 

[1] Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee;Department of Biology, Virginia Commonwealth University, Richmond; and Department of Biology, Virginia Commonwealth University, Richmond; and Department of Biology, Virginia Commonwealth University, Richmond; and

关键词: stat3;    hematopoietic;    inflammation;    caspase-3;    mitochondrial membrane potential;    immune homeostasis;   

DOI  :  10.1189/jlb.0405201

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown