Interleukin-10 modulates pro-apoptotic effects of TNF-α in human articular chondrocytes in vitro

被引：83

作者：

John, T. ^{[1
]}

Mueller, R. D. ^{[1
]}

Oberholzer, A. ^{[1
]}

Zreiqat, H. ^{[2
]}

Kohl, B. ^{[1
]}

Ertel, W. ^{[1
]}

Hostmann, A. ^{[1
]}

Tschoeke, S. K. ^{[1
]}

Schulze-Tanzil, G. ^{[1
,3
]}

机构：

[1] Charite, Dept Trauma & Reconstruct Surg, FEM, D-12207 Berlin, Germany

[2] Univ Sydney, Sch AMMEJ07, Tissue Engn & Biomat Res Unit, Sydney, NSW 2006, Australia

[3] Charite, Dept Cell & Neurobiol, Cent Anat, D-10098 Berlin, Germany

来源：

CYTOKINE | 2007年 / 40卷 / 03期

关键词：

chondrocyte; TNF-alpha; IL-10; apoptosis;

D O I：

10.1016/j.cyto.2007.10.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The aim of this study is to determine if there is an antagonistic effect between tumour necrosis factor (TNF)-alpha and the immunoregulatory interleukin (IL)-10 on chondrocytes survival. Serum-starved primary human articular chondrocytes were stimulated with either 10 ng/ml recombinant TNF-alpha, IL-10 or a combination of both (at 10 ng/ml each). Chondrocyte apoptosis was determined by measuring caspase-3/7, -8 and -9 activities using caspase assays. Mitochondrial apoptotic inducer bax, and the suppressor bcl-2 were evaluated using western blotting at 48 h. Results indicated that TNF-alpha increased caspase activities and resulted in a significant (p = 0.001) increase in bax/bcl-2 ratio. Stimulation with IL-10 did not alter caspase activities, while co-treatment with IL-10 and TNF-alpha inhibited TNF-alpha induced caspase activities and significantly (p > 0.004) impaired bax/bcl-2 ratio. At 24 h, mRNA levels for collagen type 11, TNF-ot and IL-10 were determined using real-time RT-PCR. Stimulation with TNF-ot or TNF-ot and IL-10 significantly inhibited collagen type 11 and increased IL-10 and TNF-alpha mRNA expression. IL-10 modulated the pro-apoptotic capacity of TNF-ot in chondrocytes as shown by the decrease in caspase activities and bax/bcl-2 ratio compared to TNF-ot stimulated chondrocytes, suggesting a mostly antagonistic interplay of IL-10 and TNF-ot on mitochondrial apoptotic pathways. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：226 / 234

页数：9

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