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, 2010) and prevent the increase in serum HMGB1 levels that occur during polymicrobial sepsis (Pe?a et?al., 2010); therefore, it would be interesting to investigate whether activation of AMPK by metformin is linked to JAK/STAT signals in macrophages activated with LPS or in polymicrobial sepsis. In summary, our results demonstrate, for the first time, that metformin has a therapeutic effect in an LPS-induced animal model of endotoxaemia and this effect is mediated by reducing HMGB1 release. In particular, we demonstrated that metformin treatment significantly attenuated the inflammatory response induced by LPS both in vitro and in vivo via AMPK activation. Because metformin significantly inhibited HMGB1 release in endotoxaemic mice, this effect could be the critical step for the protection of endotoxaemic animals from death. Our results indicate new targets for clinical research for the development of an effective therapy for sepsis. http://www.selleckchem.com/screening/pfizer-licensed-library.html This work was supported by a grant from NRF (03-2010-0298) and Korea Research Foundation (R13-2005-012-01003-0). No conflict of interest to report. Supporting Information: Teaching Materials; Figs 1�C8 as PowerPoint slide. Figure S1 (A) Cells were transfected with ssiRNA or treated with compC as described in Figure 5. After transfection cells were treated with http://en.wikipedia.org/wiki/Temsirolimus lipopolysaccharides (LPS) (1 ?g��mL?1) for 8 h. Then cells were harvested and subjected to immunoblotting for iNOS and ��-actin detection. Blot bands are representative of three independent experiments. (B) Cells were transfected with 1 ?g of NF-��B-luciferase plus 0.5 ?g of pRL-TK-luciferase. Cells were allowed to recover overnight and were then treated with 1 ?g��mL?1 of LPS with/without metformin (5 and 10 mM). Cells were harvested 6 h after treatment. Luciferase activities are presented as fold activation relative to that of the untreated cells. Data are presented as ��SD of three independent experiments. One-way analysis of variance was used to compare multiple group http://www.selleckchem.com/products/pifithrin-alpha.html means followed by Newman�CKeuls test (significance compared with control, **P