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Department of Parasitology and Immunology, Yamanashi Medical University, Yamanashi, Japan
Mast cells play a critical role in host immune responses and are
implicated in the pathogenesis of allergic inflammation. Though mouse
mast cell line MC/9 expresses cell surface Fas Ag and is sensitive to
Fas-induced apoptosis, activated MC/9 cells are resistant to
Fas-induced cell death by cross-linking of Fc
RI or Fc
R.
Fas-associated death domain-like IL-1-converting enzyme
(FLICE)-inhibitory protein (FLIP), a caspase-8 inhibitor that lacks the
cisteine domain, is one of the negative regulators of receptor-mediated
apoptosis. In this report, we show that activation of mast cells by
cross-linking of Fc
RI or Fc
R can induce enhanced expression of
FLIP and consequently a resistance to Fas-induced apoptosis, although
the expression level of Fas Ag is not changed. Addition of antisense
oligonucleotide for FLIP prevents resistance to Fas-induced apoptosis
of activated mast cells, suggesting that endogenous FLIP inhibits
Fas-mediated apoptosis in activated mast cells. Thus, the enhanced
expression of FLIP in activated mast cells contributes to the
resistance to Fas-induced apoptosis, which may result in the
development and prolongation of allergic
inflammation.
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