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 Google Scholar Google Scholar Articles by Pedrazzi, M. Articles by Melloni, E. Search for Related Content PubMed PubMed Citation Articles by Pedrazzi, M. Articles by Melloni, E.

Selective Proinflammatory Activation of Astrocytes by High-Mobility Group Box 1 Protein Signaling¹

Marco Pedrazzi^2,*, Mauro Patrone, Mario Passalacqua^*, Elia Ranzato, Diego Colamassaro^*, Bianca Sparatore^*, Sandro Pontremoli^* and Edon Melloni^*

^* Department of Experimental Medicine-Biochemistry Section and Centre of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, Genoa, Italy; and Department of Environmental and Life Sciences, University of Eastern Piedmont "Amedeo Avogadro", Via Bellini 25G, Alessandria, Italy

Extracellular high-mobility group box 1 protein (HMGB1) triggers inflammatory events in the brain. We demonstrate that astrocytes, the main glial cells in the brain, acquire a specific reactive phenotype when exposed to HMGB1. This cell activation, which involves the receptor for advanced glycation end-products and the MAPK/ERK1/2 cascade, results in the transcriptional/translational induction of a restricted number of inflammatory mediators, including cyclooxygenase-2, matrix metalloproteinase-9, and several chemokines of the CC and CXC families. The mixture of factors released by HMGB1-reactive astrocytes displays a potent chemotactic activity on human monocytic cells. This study is the first to suggest that HMGB1/astrocyte interaction plays a specific functional role in the progression of inflammatory processes in the CNS by facilitating local leukocyte infiltration.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Italian Ministero dell’Istruzione, dell’Università e della Ricerca (FIRB-Post Genoma Project) and by the University of Genoa, Italy.

² Address correspondence and reprint requests to Dr. Marco Pedrazzi, Department of Experimental Medicine-Biochemistry Section, University of Genoa, Viale Benedetto XV, 1-16132 Genoa, Italy. E-mail address: marcopedraz{at}libero.it

³ Abbreviations used in this paper: HMGB1, high mobility group box 1; RAGE, receptor for advanced glycation end-products; CCM, complete cytokine mixture; MMP, matrix metalloproteinase; CASP, caspase; IFIT, interferon-induced protein with tetratricopeptide repeat; IRF, interferon regulatory factor; TIMP, tissue inhibitor of the matrix metalloproteinase; COX, cyclooxygenase.