Positive and negative modulation of peptidases by pro-inflammatory cytokines

Cavazza, A. and Marini, M. and Spagnoli, G. C. and Giorgio Roda, L.. (2008) Positive and negative modulation of peptidases by pro-inflammatory cytokines. Peptides, Vol. 29, H. 1. pp. 1974-1981.

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Official URL: http://edoc.unibas.ch/dok/A6007137

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Oncology Surgery (Spagnoli)
UniBasel Contributors:Spagnoli, Giulio C.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier Science
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2013 08:29
Deposited On:08 Nov 2013 08:29

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