Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-25T02:17:50.106Z Has data issue: false hasContentIssue false

The effect of two bovine β-casein peptides on various functional properties of porcine macrophages and neutrophils: differential roles of protein kinase A and exchange protein directly activated by cyclic AMP-1

Published online by Cambridge University Press:  17 April 2007

R. Chronopoulou
Affiliation:
Department of Animal Science, Agricultural University of Athens, Athens 118 55, Greece
E. Xylouri
Affiliation:
Department of Animal Science, Agricultural University of Athens, Athens 118 55, Greece
K. Fegeros
Affiliation:
Department of Animal Science, Agricultural University of Athens, Athens 118 55, Greece
I. Politis*
Affiliation:
Department of Animal Science, Agricultural University of Athens, Athens 118 55, Greece
*
*Corresponding author: Dr Ioannis Politis, fax +30 210 529 4413, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The effects of two bovine β-casein peptides on the urokinase plasminogen activator (u-PA) system and superoxide anion (SA) production by porcine macrophages and neutrophils activated by phorbol myristate acetate (PMA) were investigated. Macrophages and neutrophils were obtained from fourteen weaned piglets and were cultured in vitro for 24h with or without one of two chemically synthesised peptides: tripeptide leucine–leucine–tyrosine (residues 191–193 of β-casein) (LLY) and hexapeptide proline–glycine–proline–isoleucine–proline–asparagine (residues 63–68 of β-casein). Following incubation, cells were stimulated with 80μM-PMA. Total cell-associated u-PA, membrane-bound u-PA, free u-PA binding sites along with SA production were determined after stimulation with PMA. Both peptides suppressed the u-PA system and SA production of PMA-stimulated macrophages isolated from piglets during weeks 1–2 after weaning. Only the tripeptide LLY suppressed the u-PA system and SA production of PMA-stimulated neutrophils during the same time period. None of the peptides tested had any effect (P>0·05) on the u-PA system and SA production of PMA-stimulated macrophages and neutrophils isolated from the same piglets during weeks 5–6 after weaning. Thus, peptides are effective only in the early post-weaning period. Using cyclic AMP analogues that are highly specific activators of protein kinase A (PKA) or exchange protein directly activated by cyclic AMP-1 (Epac-1), we found that activation of PKA, but not Epac-1, was responsible for the downregulation of the u-PA system, whereas activation of PKA an/r Epac-1 was responsible for the downregulation of SA system in both macrophages and neutrophils.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2006

References

Aronoff, DM, Canetti, C & Peters-Golden, M (2004) Prostaglandin E2 inhibits alveolar macrophage phagocytosis through an E-prostanoid 2 receptor-mediated increase in intracellular cyclic AMP. J Immunol 173, 559563.CrossRefGoogle ScholarPubMed
Aronoff, DM, Canetti, C, Serezani, C, Luo, M & Peters-Golden, M (2005) Cutting edge. Macrophage inhibition by cyclic AMP: differential roles of protein kinase A and exchange protein directly activated by cAMP-1. J Immunol 174, 595599.CrossRefGoogle ScholarPubMed
Baldi, A, Politis, I, Pecorini, C, Fusi, E, Chronopoulou, R & Dell'Orto, V (2005) Biological effects of milk proteins and their peptides with emphasis on those related to the gastrointestinal ecosystem. J Dairy Res 72, 17.CrossRefGoogle Scholar
Christensen, AE, Selheim, F, De Rooij, J, et al. (2003) cAMP analog mapping of Epac-1 and cAMP kinase: discriminating analogs demonstrate that Epac-1 and cAMP kinase act synergistically to promote PC-12 cell neurite extension. J Biol Chem 278, 3539435402.CrossRefGoogle Scholar
Clare, DA & Swaiswood, HE (2000) Bioactive milk peptides: a prospectus. J Dairy Sci 83, 11871195.CrossRefGoogle ScholarPubMed
Dent, G, Giembycz, MA, Rabe, KF, Wolf, B, Barnes, PJ & Magnussen, H (1994) Theophylline suppresses human alveolar macrophage respiratory burst through phosphodiesterase inhibition. Am J Respir Cell Mol Biol 10, 565572.CrossRefGoogle ScholarPubMed
Elitsur, Y & Luk, GD (1991) Beta-casomorphin (BCM) and human colonic lamina propria lymphocyte proliferation. Clin Exp Immunol 85, 493497.CrossRefGoogle ScholarPubMed
Enserink, JM, Christensen, AE, De Rooij, J, Van Triest, M, Schwede, F, Genieser, HG, Doskeland, OS, Blank, JL & Bos, JL (2002) A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Nat Cell Biol 4, 901906.CrossRefGoogle ScholarPubMed
Fragou, S, Fegeros, K, Xylouri, E, Baldi, A & Politis, I (2004) Effect of vitamin E supplementation on various functional properties of macrophages and neutrophils obtained from weaned piglets. J Vet Med A 51, 178183.CrossRefGoogle ScholarPubMed
Hunter, P (1986) The immune system of the neonatal and weaner piglet: a review. J S Afr Vet Assoc 57, 243245.Google ScholarPubMed
Kayser, H & Meisel, H (1996) Stimulation of human peripheral blood lymphocytes by bioactive peptides derived from bovine milk proteins. FEBS Letts 383, 1820.CrossRefGoogle ScholarPubMed
Komatsu, H, Tsukimori, K, Hata, K, Satoh, S & Nakano, H (2001) The characterization of superoxide production of human neonatal neutrophil. Early Hum Dev 65, 1119.CrossRefGoogle ScholarPubMed
Kunkel, SL, Chensue, SW & Phan, SH (1986) Prostaglandins as endogenous mediators of interleukin 1 production. J Immunol 136, 186192.CrossRefGoogle ScholarPubMed
LeBlanc, JG, Matar, C, Valdez, JC, LeBlanc, J & Perdigon, G (2002) Immunomodulating effects of peptidic fractions issued from milk fermented with Lactobacillus helveticus. J Dairy Sci 85, 27332742.CrossRefGoogle ScholarPubMed
Matar, C, Valdez, JC, Medina, M, Rachid, M & Perdigon, G (2001) The implication of proteolysis during milk fermentation on enhancing the immune system and the regression of fibrosarcomas. J Dairy Res 68, 601609.CrossRefGoogle Scholar
Meisel, H (2005) Biochemical properties of peptides encrypted in bovine milk proteins. Curr Med Chem 12, 19051919.CrossRefGoogle ScholarPubMed
Migliore-Samour, D & Jolles, P (1988) Casein, a prohormone with immunomodulating role for the newborn? Experimentia 44, 188193.CrossRefGoogle ScholarPubMed
Mustafa, SB & Olson, MS (1998) Expression of nitric-oxide synthase in rat Kupffer cells is regulated by cAMP. J Biol Chem 273, 50735080.CrossRefGoogle ScholarPubMed
Otani, H & Hata, L (1995) Inhibition of proliferative responses of mouse spleen lymphocytes and rabbit Peyer's patch cells by bovine milk caseins and their digests. J Dairy Res 62, 339348.CrossRefGoogle ScholarPubMed
Perdigon, G, Vintini, E, Alvarez, S, Medina, M & Medici, M (1999) Study of the possible mechanisms involved in the mucosal immune system activation by lactic acid bacteria. J Dairy Sci 82, 11081114.CrossRefGoogle ScholarPubMed
Pessi, T, Isolauri, E, Sutas, Y, Kankaanranta, H, Moilanen, E & Hurme, M (2001) Suppression of T-cell activation by Lactobacillus rhamnosus GG-degraded bovine casein. Immunopharmacology 1, 211218.CrossRefGoogle ScholarPubMed
Petrova, T, Alcama, K & Van Eldik, LJ (1999) Selective modulation of microglial activation by prostaglandin E2. J Biol Chem 274, 2882328827.CrossRefGoogle Scholar
Politis, I (1995) Effects of milk peptides on the immune system of dairy cows. In Reproduction and Animal Breeding: Advances and Strategy, pp. 309314 [Enne, G, Greppi, GF and Lauria, A, editors]. Paris: Elsevier.Google Scholar
Politis, I (1996) Plasminogen activator system: implications for mammary growth and involution. J Dairy Sci 79, 10971107.CrossRefGoogle ScholarPubMed
Politis, I, Hidiroglou, M, Batra, TR, Gilmore, JA, Gorewit, RC & Scherf, H (1995) Effects of vitamin E on immune function of dairy cows. Am J Vet Res 56, 179184.CrossRefGoogle ScholarPubMed
Politis, I, Voudouri, A, Bizelis, I & Zervas, G (2003) The effect of various vitamin E derivatives on the urokinase-plasminogen activator system of ovine macrophages and neutrophils. Br J Nutr 89, 259265.CrossRefGoogle ScholarPubMed
Procopio, DO, Teixeira, MM, Camargo, MM, Travassos, LR, Ferguson, MA, AlmeidaI, C & Gazzinelli, RT (1999) Differential inhibitory mechanism of cyclic AMP on TNF-alpha and IL-12 synthesis by macrophages exposed to microbial stimuli. Br J Pharmacol 127, 11951205.CrossRefGoogle ScholarPubMed
Qiao, J, Mei, FC, Popov, VL, Vergara, LA & Cheng, X (2002) Cell cycle-dependent subcellular localization of exchange factor directly activated by cAMP. J Biol Chem 19, 2658126586.CrossRefGoogle Scholar
Rowe, J, Finlay-Jones, JJ, Nicholas, TE, Bowden, J, Morton, S & Hart, PH (1997) Inability of histamine to regulate TNF-production by human alveolar macrophages. Am J Respir Cell Mol Biol 17, 218223.CrossRefGoogle Scholar
Scanlon, DB & Finlayson, J (2004) Pre/emiprep separations of peptides. Methods Mol Biol 251, 191210.Google Scholar
Tetsuka, T, Daphna-Iken, D, Srivastava, SK, Baier, LD, DuMaine, J & Morrison, AR (1994) Cross-talk between cyclooxygenase and nitric oxide pathways: prostaglandin E2 negatively modulates induction of nitric oxide synthase by interleukin 1. Proc Natl Acad Sci U S A 91, 1216812172.CrossRefGoogle ScholarPubMed
Totsuka, M, Kakehi, M, Kohyama, M, Hachimura, S, Hisatsure, T & Kaminogawa, S (1998) Enhancement of antigen-specific IFN-gamma production from CD8 (+) T cells by a single amino acid-substituted peptide derived from bovine alpha s 1-casein. Clin Immunol Immunopathol 88, 277286.CrossRefGoogle Scholar