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J Immunol. 2007 Dec 15;179(12):8525-32.

Selective proinflammatory activation of astrocytes by high-mobility group box 1 protein signaling.

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  • 1Department of Experimental Medicine-Biochemistry Section and Centre of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, Genoa, 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.

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