Costimulation with interleukin-4 and interleukin-10 induces mast cell apoptosis and cell-cycle arrest: The role of p53 and the mitochondrion

L. Andrew Bouton, Carlos D. Ramirez, Daniel P. Bailey, C. Fitzhugh Yeatman, Joyce Yue, Harry V. Wright, Jos Domen, Roberto R. Rosato, Steven Grant, Krista Fischer-Stenger, John J. Ryan

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The aim of this study was to determine the mechanism by which interleukin (IL)-4 + IL-10 costimulation regulates mast cell numbers to maintain immune homeostasis. We employed mouse bone marrow-derived mast cells (BMMC) to measure the effects of IL-4 + IL-10 on survival and cell-cycle progression. p53-Deficient, bax-deficient, and bcl-2 transgenic BMMC were compared to wild-type cells to determine the role of these proteins in apoptosis. The molecular regulation of apoptosis and cell-cycle progression was investigated using flow cytometric analysis, RNase protection, and Western blotting. IL-4 + IL-10 induced BMMC apoptosis and arrest. Apoptosis was p53-dependent. Cell death was accompanied by loss of mitochondrial membrane potential, the importance of which was demonstrated by resistance to IL-4 + IL-10-mediated cell death when Bax was deleted or Bcl-2 was overexpressed. Those cells not killed by apoptosis demonstrated a p53-independent G1 cell-cycle arrest. Apoptosis and arrest may be explained by reduced IL-3 receptor signaling. Costimulation with IL-4 + IL-10 partly controls mast cell homeostasis through a delayed apoptosis and arrest program that is induced by a blockade of IL-3 receptor signaling. The delay in these negative effects would allow the protective effects of mast cell activation to occur for several days.

Original languageEnglish (US)
Pages (from-to)1137-1145
Number of pages9
JournalExperimental Hematology
Volume32
Issue number12
DOIs
StatePublished - Dec 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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