HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Penton-Rol, G. Articles by Mantovani, A. Search for Related Content PubMed PubMed Citation Articles by Penton-Rol, G. Articles by Mantovani, A.

Bacterial Lipopolysaccharide Causes Rapid Shedding, Followed by Inhibition of mRNA Expression, of the IL-1 Type II Receptor, with Concomitant Up-Regulation of the Type I Receptor and Induction of Incompletely Spliced Transcripts^{1 ,2}

Giselle Penton-Rol^3,*, Simone Orlando^3,*, Nadia Polentarutti^*, Sergio Bernasconi^*, Marta Muzio^*, Martino Introna^* and Alberto Mantovani^4,*,

^* Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy; and Section of General Pathology, Department of Biotechnology, Università di Brescia, Brescia, Italy

The IL-1 type I receptor (IL-1RI) is part of a signaling complex together with the IL-1R accessory protein, whereas available information is consistent with a "decoy" model of function for the IL-1 type II receptor (IL-1RII). The present study was designed to investigate the effect of bacterial LPS on IL-1R in human monocytes. LPS causes rapid release of the IL-1RII, an effect blocked by a metalloprotease inhibitor. Subsequently, LPS-treated monocytes showed a drastic reduction of IL-1RII mRNA. In contrast, LPS induced IL-1RI and, to a lesser extent, IL-1AcP expression. LPS-induced augmented expression of the canonical 5-kb IL-1RI mRNA was accompanied by the appearance of 2.4-kb IL-1RI transcripts. The use of probes representative of different regions of the IL-1RI mRNA, as well as cDNA cloning, revealed that the 2.4-kb inducible band includes incompletely spliced, polyadenylated transcripts potentially encoding truncated versions of the receptor. The observation that the prototypic proinflammatory molecule LPS has divergent effects on IL-1Rs, with inhibition of IL-1RII and stimulation of IL-1RI and IL-1R accessory protein, is consistent with the view that these molecules subserve opposite functions in the pathophysiology of the IL-1 system. The rapid shedding of IL-1RII by monocytes early in recruitment may serve to buffer the systemic action of IL-1 leaking from sites of inflammation. This early event, followed by prolonged inhibition of IL-1RII expression and up-regulation of IL-1RI, may render monocytes more responsive to IL-1 at sites of inflammation.

This article has been cited by other articles:

				X. Huang, L. D. Hazlett, W. Du, and R. P. Barrett SIGIRR Promotes Resistance against Pseudomonas aeruginosa Keratitis by Down-Regulating Type-1 Immunity and IL-1R1 and TLR4 Signaling J. Immunol., July 1, 2006; 177(1): 548 - 556. [Abstract] [Full Text] [PDF]

				G. Verbruggen Chondroprotective drugs in degenerative joint diseases Rheumatology, February 1, 2006; 45(2): 129 - 138. [Abstract] [Full Text] [PDF]

				M. Huber-Lang, J. V. Sarma, D. Rittirsch, H. Schreiber, M. Weiss, M. Flierl, E. Younkin, M. Schneider, H. Suger-Wiedeck, F. Gebhard, et al. Changes in the Novel Orphan, C5a Receptor (C5L2), during Experimental Sepsis and Sepsis in Humans J. Immunol., January 15, 2005; 174(2): 1104 - 1110. [Abstract] [Full Text] [PDF]

				X. Cui, F. N. Rouhani, F. Hawari, and S. J. Levine Shedding of the Type II IL-1 Decoy Receptor Requires a Multifunctional Aminopeptidase, Aminopeptidase Regulator of TNF Receptor Type 1 Shedding J. Immunol., December 15, 2003; 171(12): 6814 - 6819. [Abstract] [Full Text] [PDF]

				J. M. Prevost, J. L. Pelley, W. Zhu, G. E. D'Egidio, P. P. Beaudry, C. Pihl, G. G. Neely, E. Claret, J. Wijdenes, and C. B. Brown Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) and Inflammatory Stimuli Up-Regulate Secretion of the Soluble GM-CSF Receptor in Human Monocytes: Evidence for Ectodomain Shedding of the Cell Surface GM-CSF Receptor {alpha} Subunit J. Immunol., November 15, 2002; 169(10): 5679 - 5688. [Abstract] [Full Text] [PDF]

				B. Muller, G. Peri, A. Doni, A. P. Perruchoud, R. Landmann, F. Pasqualini, and A. Mantovani High circulating levels of the IL-1 type II decoy receptor in critically ill patients with sepsis: association of high decoy receptor levels with glucocorticoid administration J. Leukoc. Biol., October 1, 2002; 72(4): 643 - 649. [Abstract] [Full Text] [PDF]

				K. A. Hintz, A. J. Rassias, K. Wardwell, M. L. Moss, P. M. Morganelli, P. A. Pioli, A. L. Givan, P. K. Wallace, M. P. Yeager, and P. M. Guyre Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163 J. Leukoc. Biol., October 1, 2002; 72(4): 711 - 717. [Abstract] [Full Text] [PDF]

				M. Muzio, D. Bosisio, N. Polentarutti, G. D'amico, A. Stoppacciaro, R. Mancinelli, C. van't Veer, G. Penton-Rol, L. P. Ruco, P. Allavena, et al. Differential Expression and Regulation of Toll-Like Receptors (TLR) in Human Leukocytes: Selective Expression of TLR3 in Dendritic Cells J. Immunol., June 1, 2000; 164(11): 5998 - 6004. [Abstract] [Full Text] [PDF]

				L. E. Jensen, M. Muzio, A. Mantovani, and A. S. Whitehead IL-1 Signaling Cascade in Liver Cells and the Involvement of a Soluble Form of the IL-1 Receptor Accessory Protein ,2 J. Immunol., May 15, 2000; 164(10): 5277 - 5286. [Abstract] [Full Text] [PDF]

				J. M. Daun, R. W. Ball, and J. G. Cannon Glucocorticoid sensitivity of interleukin-1 agonist and antagonist secretion: the effects of age and gender Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2000; 278(4): R855 - R862. [Abstract] [Full Text] [PDF]