当前位置： SCI文献检索 > IMMUNOLOGY LETTERS期刊下所有文献 > Rapid up-regulation of c-FLIP expression by BCR signaling through the PI3K/Akt pathway inhibits simultaneously induced Fas-mediated apoptosis in murine B lymphocytes.

Rapid up-regulation of c-FLIP expression by BCR signaling through the PI3K/Akt pathway inhibits simultaneously induced Fas-mediated apoptosis in murine B lymphocytes.

Abstract：

:Cross-linking of BCR rapidly induces protection of B cells from Fas-mediated apoptosis, which has been assumed one of the important survival mechanisms of B cells during antigen stimulation. In the mouse B cell line A20, which is sensitive to Fas-mediated apoptosis, stimulation of BCR inhibited apoptosis induced via Fas upstream of caspase-8 activation with an associated rapid increase in the expression of both short and long forms of cellular caspase-8/FLICE-inhibitory protein (c-FLIP). The c-FLIP competitively inhibited the recruitment of caspase-8 to the death-inducing signaling complex (DISC), which took as long as 3h to form after the stimulation of Fas in A20 cells. Knockdown of c-FLIP by a short hairpin RNA-expressing method rendered BCR-stimulated A20 cells sensitive to Fas-mediated apoptosis. The BCR-induced rapid expression of c-FLIP was not affected by inactivation of NF-kappaB, but was inhibited by either treatment with a PI3K inhibitor, LY294002, or expression of a dominant negative PI3K p85 subunit, both of which suppressed phosphorylation of Akt and sensitized BCR-stimulated A20 cells to Fas-mediated apoptosis. Overexpression of constitutively active Akt was shown not only to up-regulate c-FLIP expression but also to render A20 cells resistant to Fas-mediated apoptosis. Moreover, treatment with LY294002 also suppressed BCR-induced up-regulation of c-FLIP expression in spleen B cells. Taken together, BCR-stimulation was shown to rapidly trigger a survival signal against simultaneously or ongoingly stimulated Fas-mediated apoptosis by promoting a PI3K/Akt signaling pathway-mediated up-regulation of c-FLIP expression.

journal_name

Immunol Lett

journal_title

Immunology letters

authors

Moriyama H,Yonehara S

doi

10.1016/j.imlet.2006.12.009

subject

Has Abstract

pub_date

2007-03-15 00:00:00

pages

36-46

issue

1

eissn

0165-2478

issn

1879-0542

pii

S0165-2478(07)00005-3

journal_volume

109

pub_type

杂志文章

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