Effect of IL-1 on the hydrolysis of the tumor antigen epitope gp100(280-288) by fibroblast-expressed enzymes.
The role of proinflammatory cytokines in increasing the activity of specific proteases suggests the hypothesis that, by altering the expression of these mediators, adjuvants may modulate the effectiveness of peptides used as vaccines. The possible effect of IL-1 on fibroblast-expressed, peptidases was, thus, investigated by analyzing the degradation of a tumor antigen epitope (gp100(280-288), YLEPGPVTA) in the presence of cultured human fibroblasts. The data obtained indicate an increase of substrate hydrolysis after IL-1 treatment as compared with non-treated controls. Hydrolysis increase was accompanied by defined changes in the population of the by-products formed: specifically, the amount of peptidic by-products increased more than the amount of single amino acids, and the amount of the C-terminal by-products increased more than the amount of their N-terminal counterpart. These data appear to indicate that the positive effect of IL-1 on the activity of substrate-active enzymes is function of modified expression of a number of these enzymes by fibroblasts. From these data it can be inferred that the use of IL-1-inducing adjuvants, increasing the activity of peptidases expressed by bystander cells, may reduce the bio-availability of peptides used for immunization.
Cavazza
Antonella
A
Dipartimento di Neuroscienze, Università degli Studi di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Marini
Mario
M
Spagnoli
Giulio C
GC
Roda
L Giorgio
LG
D000596:Amino Acids / Q000032:analysis; D002853:Chromatography, Liquid; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000378:metabolism*; D010455:Peptides; D058951:gp100 Melanoma Antigen
D000596:Amino Acids; D016895:Culture Media, Serum-Free; D007375:Interleukin-1; D008562:Membrane Glycoproteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D010455:Peptides; D058951:gp100 Melanoma Antigen; C548641:gp100(280-288) melanoma antigen peptide; D010447:Peptide Hydrolases