Enhanced Expression of Fas-Associated Death Domain-Like IL-1-Converting Enzyme (FLICE)-Inhibitory Protein Induces Resistance to Fas-Mediated Apoptosis in Activated Mast Cells
Enhanced Expression of Fas-Associated Death Domain-Like IL-1-Converting Enzyme (FLICE)-Inhibitory Protein Induces Resistance to Fas-Mediated Apoptosis in Activated Mast Cells
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Fas 相关死亡结构域样 IL-1 转换酶 (FLICE) 抑制蛋白的增强表达可诱导激活的肥大细胞对 Fas 介导的细胞凋亡的抵抗
作者：
H. Yoshikawa;Y. Nakajima;K. Tasaka
肥大细胞在宿主免疫应答中起关键作用，并与过敏性炎症的发病机制有关。虽然小鼠肥大细胞系MC/9表达细胞表面Fas Ag，对Fas诱导的细胞凋亡敏感，但活化的MC/9细胞通过FcεRI或FcγR的交联而抵抗Fas诱导的细胞死亡。Fas相关死亡结构域样IL-1转化酶（FLICE）抑制蛋白（FLIP）是一种缺乏半胱氨酸结构域的caspase-8抑制剂，是受体介导的细胞凋亡的负调节因子之一。在本报告中，我们发现通过FcεRI或FcγR的交联激活肥大细胞可以诱导FLIP表达增强，从而抵抗Fas诱导的凋亡，尽管Fas Ag的表达水平没有改变。添加FLIP的反义寡核苷酸阻止活化肥大细胞对Fas诱导的凋亡的抵抗，表明内源性FLIP抑制活化肥大细胞中Fas介导的凋亡。因此，FLIP在活化的肥大细胞中的表达增强有助于抵抗Fas诱导的凋亡，这可能导致过敏性炎症的发展和延长。
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 FcεRI or FcγR. 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 FcεRI or FcγR 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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Bcl-x 保护原代 B 细胞免受 Fas 介导的细胞凋亡。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Schneider,TJ;Grillot,D;Foote,LC;Núñez,GE;Rothstein,TL
通讯作者：
Rothstein,TL
影响因子：
4.4
作者：
Rie Watanabe‐Fukunaga;C. Brannan;N. Itoh;S. Yonehara;N. Copeland;N. Jenkins;S. Nagata
通讯作者：
Rie Watanabe‐Fukunaga;C. Brannan;N. Itoh;S. Yonehara;N. Copeland;N. Jenkins;S. Nagata
影响因子：
32.4
作者：
Hitoshi, Y;Lorens, J;Nolan, GP
通讯作者：
Nolan, GP
影响因子：
32.4
作者：
Refaeli, Y;Van Parijs, L;Abbas, AK
通讯作者：
Abbas, AK
DOI：
10.1073/pnas.88.9.3671
发表时间：
1991-05-01
影响因子：
11.1
作者：
SMILEY, ST;REERS, M;CHEN, LB
通讯作者：
CHEN, LB