Positive and negative modulation of peptidases by pro-inflammatory cytokines

被引:0
|
作者
Cavazza, Antonella [2 ]
Marini, Mario [1 ]
Spagnoli, Giulio C. [3 ,4 ]
Roda, L. Giorgio [1 ]
机构
[1] Univ Roma Tor Vergata, Dipartimento Neurosci, I-00133 Rome, Italy
[2] Univ Parma, Dipartimento Chim Gen & Inorgan, I-43100 Parma, Italy
[3] Univ Basel, ICFS, Basel, Switzerland
[4] Univ Basel, Dept Forsch, Basel, Switzerland
关键词
Cytokines; Proteolysis; Human fibroblasts;
D O I
10.1016/j.peptides.2008.06.018
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 capacity of pro-inflammatory cytokines to modulate proteolysis was analyzed by liquid chromatography using human fibroblasts as cell model and enzyme source, and the immunodominant epitope gp100(280-288) (YLEPGPVTA) as substrate. The measurements made after fibroblast pre-incubation with either IL-1, TNF, or IL-6 plus its soluble receptors have been compared with those made with un-stimulated fibroblasts. The results obtained suggest an uneven association of cytokine treatment with substrate degradation, and with a prevailingly positive - but also negative - association with release of smaller peptides and free amino acids. Data obtained by separately measuring these two groups of by-products indicate that, after IL-1 cell pre-treatment, the velocity of formation of both groups of by-products increased, resulting in a net increase of substrate degradation. After TNF and IL-6 pre-treatment, the increase of one group was compensated by a decrease of the other group; specifically, the compensation was only partial for TNF, and overall substrate hydrolysis increased. in the case of IL-6, the increase of free amino acids was almost exactly compensated by a reduction of peptidic by-products, resulting in a negligible increase of substrate hydrolysis. In addition, the existence of reaction time-related modifications in the apparent velocity of substrate degradation and formation of by-products, allows hypothesizing different effects of cytokines on the enzymes degrading the substrate with different time constants. Taken together, these data can be interpreted as indicating different, positive and negative, effects of the three cytokines on the individual enzymes expressed by fibroblasts and capable of degrading peptidic substrates. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:1974 / 1981
页数:8
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