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首页> 外文期刊>Rheumatology international. >Expression of Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (FLIP) in human articular chondrocytes: possible contribution to the resistance to Fas-mediated death of in vitro cultured human articular c
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Expression of Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (FLIP) in human articular chondrocytes: possible contribution to the resistance to Fas-mediated death of in vitro cultured human articular c

机译:Fas相关死亡域样白介素-1β转换酶(FLICE)抑制蛋白(FLIP)在人关节软骨细胞中的表达:可能对体外培养的人关节软骨对Fas介导的死亡的抵抗力做出贡献

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摘要

Although chondrocyte apoptosis has been noted in arthritic joints, the mechanism is not clear. To investigate whether Fas-mediated apoptosis has a role in this process, the presence of Fas mRNA and expression of cell surface Fas protein in monolayer-cultured human articular chondrocytes was analyzed. Fas mRNA was found in all chondrocyte samples analyzed; moreover, the majority of cells in chondrocyte populations expressed cell-surface Fas (12-90%, average 49%). Nevertheless, treatment with an agonistic anti-Fas antibody did not induce significant apoptosis in these chondrocytes in vitro. However, it was also found that chondrocytes express Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (FLIP), a molecule which blocks Fas-mediated apoptosis. Correspondingly, activation of caspase-8 was minimal in these cultured chondrocytes. In conclusion, although human articular chondrocytes do express cell-surface Fas, this receptor did not fully mediate death-inducing signals in vitro. This resistance to Fas may be partly due to the constitutive expression of FLIP.
机译:尽管在关节炎的关节中已注意到软骨细胞凋亡,但其机制尚不清楚。为了研究Fas介导的凋亡是否在此过程中起作用,分析了Fas mRNA的存在和单层培养的人关节软骨细胞中细胞表面Fas蛋白的表达。在所分析的所有软骨细胞样本中均发现了Fas mRNA。此外,软骨细胞群中的大多数细胞表达细胞表面Fas(12-90%,平均49%)。然而,在体外,用激动性抗-Fas抗体治疗并没有在这些软骨细胞中诱导明显的细胞凋亡。但是,还发现软骨细胞表达与Fas相关的死亡域样白介素-1β转换酶抑制蛋白(FLIP),该分子可阻断Fas介导的细胞凋亡。相应地,在这些培养的​​软骨细胞中,caspase-8的激活作用最小。总之,尽管人类关节软骨细胞确实表达细胞表面Fas,但该受体并未在体外完全介导死亡诱导信号。这种对Fas的抗性可能部分归因于FLIP的组成型表达。

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