Selective proinflammatory activation of astrocytes by high-mobility group box 1 protein signaling.
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.
Department of Experimental Medicine-Biochemistry Section and Centre of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, Genoa, Italy. marcopedraz@libero.it
Marco
M
Pedrazzi
Mauro
M
Patrone
Mario
M
Passalacqua
Elia
E
Ranzato
Diego
D
Colamassaro
Bianca
B
Sparatore
Sandro
S
Pontremoli
Edon
E
Melloni
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004660:Encephalitis / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects; D024243:HMGB1 Protein / Q000378:metabolism* / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism; D045726:Metalloproteases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
D018925:Chemokines; D024243:HMGB1 Protein; D011994:Recombinant Proteins; D045726:Metalloproteases