Costimulation with interleukin-4 and interleukin-10 induces mast cell apoptosis and cell-cycle arrest: the role of p53 and the mitochondrion.
Exp Hematol
; 32(12): 1137-45, 2004 Dec.
Article
em En
| MEDLINE
| ID: mdl-15588938
ABSTRACT
OBJECTIVE:
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. MATERIALS ANDMETHODS:
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.RESULTS:
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.CONCLUSION:
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.
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Base de dados:
MEDLINE
Assunto principal:
Fase G1
/
Proteína Supressora de Tumor p53
/
Interleucina-4
/
Interleucina-10
/
Apoptose
/
Mastócitos
/
Mitocôndrias
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article