Antiinflammatory properties of hepatic acute phase proteins: preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1 beta synthesis by human peripheral blood mononuclear cells

doi:10.1084/jem.178.5.1629

This Article

	Full Text (PDF, 629K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Tilg, H.
	Articles by Mier, J. W.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Tilg, H.
	Articles by Mier, J. W.


Social Bookmarking

	What's this?

ARTICLES

Antiinflammatory properties of hepatic acute phase proteins: preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1 beta synthesis by human peripheral blood mononuclear cells

H Tilg, E Vannier, G Vachino, CA Dinarello and JW Mier
Department of Medicine, New England Medical Center, Boston, Massachusetts.

This study was undertaken to determine whether acute phase proteins (APP) induce the synthesis of interleukin 1 beta (IL-1 beta) and its specific antagonist, IL-1 receptor antagonist (IL-1Ra), in human peripheral blood mononuclear cells (PBMC). PBMC from healthy volunteers were incubated with C-reactive protein (CRP), alpha 1-antitrypsin (alpha 1-AT), or alpha 1-acid glycoprotein (AGP), and the levels of IL- 1 beta and IL-1Ra produced were measured by specific radioimmunoassay. To evaluate the effects of alpha 1-AT further, a synthetic pentapeptide FVYLI corresponding to the minimal binding sequence for the serpine- enzyme complex receptor was also evaluated. PBMC incubated for 24 h with CRP, alpha 1-AT, or the pentapeptide FVYLI synthesized large quantities of IL-1Ra, 5-10-fold greater than the amount of IL-1 beta produced by these cells. AGP induced significantly less IL-1Ra than the other APP tested. These effects were shown to be specific, in that polyclonal antibodies against CRP, alpha 1-AT, and AGP eliminated the cytokine production induced by these respective proteins. CRP, alpha 1- AT, FVYLI, and AGP were synergistic with low concentrations of endotoxin in the induction of both IL-1Ra and IL-1 beta synthesis. We suggest that the preferential induction of IL-1Ra by APP may contribute to their antiinflammatory effects and provide an important regulatory signal for the acute phase response.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Lewis, E. C., Mizrahi, M., Toledano, M., DeFelice, N., Wright, J. L., Churg, A., Shapiro, L., Dinarello, C. A. (2008). {alpha}1-Antitrypsin monotherapy induces immune tolerance during islet allograft transplantation in mice. Proc. Natl. Acad. Sci. USA 105: 16236-16241 [Abstract] [Full Text]
Huntoon, K. M., Wang, Y., Eppolito, C. A., Barbour, K. W., Berger, F. G., Shrikant, P. A., Baumann, H. (2008). The acute phase protein haptoglobin regulates host immunity. J. Leukoc. Biol. 84: 170-181 [Abstract] [Full Text]
Rahman, S. H., Evans, J., Toogood, G. J., Lodge, P. A., Prasad, K. R. (2008). Prognostic Utility of Postoperative C-reactive Protein for Posthepatectomy Liver Failure. Arch Surg 143: 247-253 [Abstract] [Full Text]
Mold, C., Du Clos, T. W. (2006). C-Reactive Protein Increases Cytokine Responses to Streptococcus pneumoniae through Interactions with Fc{gamma} Receptors.. J. Immunol. 176: 7598-7604 [Abstract] [Full Text]
Theilgaard-Monch, K., Jacobsen, L. C., Rasmussen, T., Niemann, C. U., Udby, L., Borup, R., Gharib, M., Arkwright, P. D., Gombart, A. F., Calafat, J., Porse, B. T., Borregaard, N. (2005). Highly glycosylated {alpha}1-acid glycoprotein is synthesized in myelocytes, stored in secondary granules, and released by activated neutrophils. J. Leukoc. Biol. 78: 462-470 [Abstract] [Full Text]
Black, S., Kushner, I., Samols, D. (2004). C-reactive Protein. J. Biol. Chem. 279: 48487-48490 [Abstract] [Full Text]
Fransson, B. A., Karlstam, E., Bergstrom, A., Lagerstedt, A.-S., Park, J. S., Evans, M. A., Ragle, C. A. (2004). C-reactive Protein in the Differentiation of Pyometra From Cystic Endometrial Hyperplasia/Mucometra in Dogs. Journal of the American Animal Hospital Association 40: 391-399 [Abstract] [Full Text]
Bode, J. G., Schweigart, J., Kehrmann, J., Ehlting, C., Schaper, F., Heinrich, P. C., Haussinger, D. (2003). TNF-{alpha} Induces Tyrosine Phosphorylation and Recruitment of the Src Homology Protein-Tyrosine Phosphatase 2 to the gp130 Signal-Transducing Subunit of the IL-6 Receptor Complex. J. Immunol. 171: 257-266 [Abstract] [Full Text]
Mold, C., Rodriguez, W., Rodic-Polic, B., Du Clos, T. W. (2002). C-Reactive Protein Mediates Protection from Lipopolysaccharide Through Interactions With Fc{gamma}R. J. Immunol. 169: 7019-7025 [Abstract] [Full Text]
Barbour, K. W., Goodwin, R. L., Guillonneau, F., Wang, Y., Baumann, H., Berger, F. G. (2002). Functional Diversification During Evolution of the Murine {alpha}1-Proteinase Inhibitor Family: Role of the Hypervariable Reactive Center Loop. Mol Biol Evol 19: 718-727 [Abstract] [Full Text]
Bode, J. G., Fischer, R., Haussinger, D., Graeve, L., Heinrich, P. C., Schaper, F. (2001). The Inhibitory Effect of IL-1{beta} on IL-6-Induced {alpha}2-Macroglobulin Expression Is Due to Activation of NF-{kappa}B. J. Immunol. 167: 1469-1481 [Abstract] [Full Text]
Dias, A. A. M., Goodman, A. R., Dos Santos, J. L., Gomes, R. N., Altmeyer, A., Bozza, P. T., de Fatima Horta, M., Vilcek, J., Reis, L. F. L. (2001). TSG-14 transgenic mice have improved survival to endotoxemia and to CLP-induced sepsis. J. Leukoc. Biol. 69: 928-936 [Abstract] [Full Text]
Daemen, M. A. R. C., Heemskerk, V. H., van 't Veer, C., Denecker, G., Wolfs, T. G. A. M., Vandenabeele, P., Buurman, W. A. (2000). Functional Protection by Acute Phase Proteins {alpha}1-Acid Glycoprotein and {alpha}1-Antitrypsin Against Ischemia/Reperfusion Injury by Preventing Apoptosis and Inflammation. Circulation 102: 1420-1426 [Abstract] [Full Text]
Fournier, T., Bouach, N., Delafosse, C., Crestani, B., Aubier, M. (1999). Inducible Expression and Regulation of the {alpha}1-Acid Glycoprotein Gene by Alveolar Macrophages: Prostaglandin E2 and Cyclic AMP Act as New Positive Stimuli. J. Immunol. 163: 2883-2890 [Abstract] [Full Text]
van den Berg, R. H., Faber-Krol, M. C., Sim, R. B., Daha, M. R. (1998). The First Subcomponent of Complement, C1q, Triggers the Production of IL-8, IL-6, and Monocyte Chemoattractant Peptide-1 by Human Umbilical Vein Endothelial Cells. J. Immunol. 161: 6924-6930 [Abstract] [Full Text]
Mackowiak, P. A. (1998). Concepts of Fever. Arch Intern Med 158: 1870-1881 [Abstract] [Full Text]
Crestani, B., Rolland, C., Lardeux, B., Fournier, T., Bernuau, D., Pous, C., Vissuzaine, C., Li, L., Aubier, M. (1998). Inducible Expression of the {alpha}1-Acid Glycoprotein by Rat and Human Type II Alveolar Epithelial Cells. J. Immunol. 160: 4596-4605 [Abstract] [Full Text]
Xia, D., Samols, D. (1997). Transgenic mice expressing rabbit C-reactive protein are resistant to�endotoxemia. Proc. Natl. Acad. Sci. USA 94: 2575-2580 [Abstract] [Full Text]
Lagrand, W. K., Niessen, H. W.M., Wolbink, G.-J., Jaspars, L. H., Visser, C. A., Verheugt, F. W.A., Meijer, C. J.L.M., Hack, C. E. (1997). C-Reactive Protein Colocalizes With Complement in Human Hearts During Acute Myocardial Infarction. Circulation 95: 97-103 [Abstract] [Full Text]