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Titre du document / Document title

Cytokine-inducing activity of a proline-rich polypeptide complex (PRP) from ovine colostrum and its active nonapeptide fragment analogs

Auteur(s) / Author(s)

ZABŁOCKA Agnieszka (1) ; JANUSZ Maria (1) ; RYBKA Katarzyna (1) ; WIRKUS-ROMANOWSKA Irena (2) ; KUPRYSZEWSKI Gotfryd (2) ; LISOWSKI Jozef (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, POLOGNE
(2) Faculty of Chemistry, Gdańsk University, Gdańsk, POLOGNE

Résumé / Abstract

A complex of proline-rich polypeptides (PRP) was isolated from ovine colostrum in our laboratory and was shown to possess immunomodulatory properties and psychotropic activity, including beneficial effects in the treatment of Alzheimer's disease. A nonapeptide fragment (NP): Val-Glu-Ser-Tyr-Val-Pro-Leu-Phe-Pro, isolated from the chymotryptic digestion products of PRP, and its C-terminal fragment, a hexapeptide (HP): Tyr-Val-Pro-Leu-Phe-Pro also exhibited immunoregulatory activity. Although NP and HP expressed activity similar to that of PRP in studies on humoral and cellular immune responses, in other immune processes, e.g. induction of cytokines, they showed markedly lower activity than PRP. In the search for more active peptides, in the present study, we compared the cytokine-inducing ability of PRP, NP, HP, and linear oligomers of NP or HP. For this purpose, the induction of IFN, TNF-a, IL-6, and IL-10 in human whole blood cell cultures was measured. NP, HP, and their oligomers showed differential effects in the induction of cytokines, generally lower than that of PRP. Only the PRP complex showed a bell-shaped dose-response dependence suggesting regulatory properties. There were no distinct differences between monomeric forms of NP (NP1) or HP (HP1) and their oligomers in the induction of IFN and TNF-α (Th1 cytokines) but such differences were found in the induction of IL-6 and IL-10 (Th2 cytokines). Dimer (NP2) was less active than the monomeric NP1 nonapeptide in the induction of IL-6 and IL-10. On the other hand, oligomers: HP3 and HP4, showed a significantly higher ability to induce Th2 cytokines compared to HP1, HP2 or NP peptides. This was especially evident in the case of IL-10 induction, where the activity of HP4surpassed the activity of PRP and approached the activity of LPS-PHA. The results obtained showed that some of the peptides studied, when used at higher concentrations (100 μg/ml) may replace the PRP complex as cytokine inducers. Our data also suggest the possibility of using certain oligomers for selective induction of particular cytokines.

Revue / Journal Title

European cytokine network    ISSN  1148-5493 

Source / Source

2001, vol. 12, no3, pp. 462-467 (35 ref.)

Langue / Language

Anglais

Editeur / Publisher

Libbey-Eurotext, Montrouge, FRANCE  (1990) (Revue)

Mots-clés anglais / English Keywords

Cytokine

;

Degenerative disease

;

Cerebral disorder

;

Central nervous system disease

;

Nervous system diseases

;

Human

;

Immune regulation

;

Biological activity

;

Analog

;

Molecular structure

;

Interleukin 6

;

Interferon

;

Tumor necrosis factor α

;

Interleukin 10

;

Immune response

;

Monomer

;

Oligomer

;

Hexapeptide

;

Nonapeptide

;

Proline

;

Polypeptide

;

Colostrum

;

Alzheimer disease

;

Mots-clés français / French Keywords

Cytokine

;

Maladie dégénérative

;

Encéphale pathologie

;

Système nerveux central pathologie

;

Système nerveux pathologie

;

Homme

;

Immunorégulation

;

Activité biologique

;

Analogue

;

Structure moléculaire

;

Interleukine 6

;

Interféron

;

Facteur nécrose tumorale α

;

Interleukine 10

;

Réponse immune

;

Monomère

;

Oligomère

;

Hexapeptide

;

Nonapeptide

;

Proline

;

Polypeptide

;

Colostrum

;

Démence Alzheimer

;

Mots-clés espagnols / Spanish Keywords

Citoquina

;

Enfermedad degenerativa

;

Encéfalo patología

;

Sistema nervosio central patología

;

Sistema nervioso patología

;

Hombre

;

Inmunoregulación

;

Actividad biológica

;

Análogo

;

Estructura molecular

;

Interleuquina 6

;

Interferón

;

Factor necrosis tumoral α

;

Interleuquina 10

;

Respuesta inmune

;

Monómero

;

Oligómero

;

Hexapéptido

;

Nonapéptido

;

Prolina

;

Polipéptido

;

Calostro

;

Demencia Alzheimer

;

Localisation / Location

INIST-CNRS, Cote INIST : 22500, 35400009593931.0100

Nº notice refdoc (ud4) : 14117670



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