Published online before print February 3, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0905493v1 79/4/797    most recent Alert me when this article is cited Alert me if a correction is posted 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 Doni, A. Articles by Mantovani, A. Search for Related Content PubMed PubMed Citation Articles by Doni, A. Articles by Mantovani, A.

(Journal of Leukocyte Biology. 2006;79:797-802.)
© 2006 by Society for Leukocyte Biology

Regulation of PTX3, a key component of humoral innate immunity in human dendritic cells: stimulation by IL-10 and inhibition by IFN-

Andrea Doni^*, Mosca Michela, Barbara Bottazzi^*, Giuseppe Peri^*, Sonia Valentino^*, Nadia Polentarutti^*, Cecilia Garlanda^* and Alberto Mantovani^*,,1

^* Istituto Clinico Humanitas (ICH), Rozzano, Milan, Italy;
Department of Experimental Medicine and Public Health, University of Camerino, Macerata, Italy; and
Institute of General Pathology, University of Milan, Italy

¹Correspondence: Istituto Clinico Humanitas (ICH), via Manzoni, 56 20089 Rozzano, Milan, Italy. E-mail: alberto.mantovani{at}humanitas.it

The protopypic long pentraxin 3 (PTX3) is a unique, humoral pattern-recognition receptor, which plays a nonredundant function in innate resistance to pathogens. Dendritic cells (DC) of myelomonocytic origin, but not plasmacytoid DC, are a major source of PTX3 in response to Toll-like receptor (TLR) engagment. The present study was designed to explore the regulation of PTX3 production in DC. PTX3 production was induced by TLR ligands, CD40 ligand, and interleukin (IL)-1ß and was suppressed by dexamethasone, 1, 25-dihydroxivitamin D₃, and prostaglandin E₂. It was unexpected that lipopolysaccharide (LPS)-stimulated PTX3 production was enhanced by IL-10 and inhibited by IL-4 and interferon- (IFN-). Enhancement of PTX3 production by IL-10 was also evident when Pam₃ Cys-Ser-(Lys)₄.3HCl, a TLR2-TLR1 agonist, polyionisicpolycytidylic acid, a TLR3 agonist, and IL-1ß were used as stimuli. The effect of IL-10 was blocked by an anti-IL-10 monoclonal antibody (mAb) or an anti-IL-10 receptor mAb, which also reduced the LPS-induced production. Thus, production of PTX3 in DC is subjected to a distinct regulatory network, with inhibition by IFN- and enhancement by IL-10. The amplification by IL-10 of production of a nonredundant component of fluid-phase innate immunity mirrors the IL-10 stimulatory function on B cells in adaptive immunity. As PTX3 is also an extracellular matrix component, IL-10-enhanced PTX3 production may play a role in orchestration of tissue remodeling in chronic inflammation.

Key Words: pentraxins • cytokines • tissue remodeling

This article has been cited by other articles:

				V. Maina, A. Cotena, A. Doni, M. Nebuloni, F. Pasqualini, C. M. Milner, A. J. Day, A. Mantovani, and C. Garlanda Coregulation in human leukocytes of the long pentraxin PTX3 and TSG-6 J. Leukoc. Biol., July 1, 2009; 86(1): 123 - 132. [Abstract] [Full Text] [PDF]

				L. Deban, H. Jarva, M. J. Lehtinen, B. Bottazzi, A. Bastone, A. Doni, T. S. Jokiranta, A. Mantovani, and S. Meri Binding of the Long Pentraxin PTX3 to Factor H: Interacting Domains and Function in the Regulation of Complement Activation J. Immunol., December 15, 2008; 181(12): 8433 - 8440. [Abstract] [Full Text] [PDF]

				H. Wan, C. G. van Helden-Meeuwsen, C. Garlanda, L. M. E. Leijten, V. Maina, N. A. Khan, H. A. Drexhage, A. Mantovani, R. Benner, and M. A. Versnel Chorionic gonadotropin up-regulates long pentraxin 3 expression in myeloid cells J. Leukoc. Biol., November 1, 2008; 84(5): 1346 - 1352. [Abstract] [Full Text] [PDF]

				A. Doni, G. Mantovani, C. Porta, J. Tuckermann, H. M. Reichardt, A. Kleiman, M. Sironi, L. Rubino, F. Pasqualini, M. Nebuloni, et al. Cell-specific Regulation of PTX3 by Glucocorticoid Hormones in Hematopoietic and Nonhematopoietic Cells J. Biol. Chem., October 31, 2008; 283(44): 29983 - 29992. [Abstract] [Full Text] [PDF]

				G. D. Norata, P. Marchesi, A. Pirillo, P. Uboldi, G. Chiesa, V. Maina, C. Garlanda, A. Mantovani, and A. L. Catapano Long Pentraxin 3, a Key Component of Innate Immunity, Is Modulated by High-Density Lipoproteins in Endothelial Cells Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 925 - 931. [Abstract] [Full Text] [PDF]

				A. Inforzato, V. Rivieccio, A. P. Morreale, A. Bastone, A. Salustri, L. Scarchilli, A. Verdoliva, S. Vincenti, G. Gallo, C. Chiapparino, et al. Structural Characterization of PTX3 Disulfide Bond Network and Its Multimeric Status in Cumulus Matrix Organization J. Biol. Chem., April 11, 2008; 283(15): 10147 - 10161. [Abstract] [Full Text] [PDF]

				X. He, B. Han, and M. Liu Long pentraxin 3 in pulmonary infection and acute lung injury Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1039 - L1049. [Abstract] [Full Text] [PDF]

				S. Jaillon, G. Peri, Y. Delneste, I. Fremaux, A. Doni, F. Moalli, C. Garlanda, L. Romani, H. Gascan, S. Bellocchio, et al. The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps J. Exp. Med., April 16, 2007; 204(4): 793 - 804. [Abstract] [Full Text] [PDF]