2012
DOI: 10.1007/s00011-012-0442-x
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HSP90 inhibition by 17-DMAG reduces inflammation in J774 macrophages through suppression of Akt and nuclear factor-κB pathways

Abstract: Our studies show that the immune-mediated NF-κB inflammatory cascade is blocked by the HSP90 inhibitor 17-DMAG. Due to the broad interaction of HSP90 with many pro-inflammatory kinase cascades, inhibition of HSP90 may provide a novel approach to reducing chronic inflammation.

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Cited by 51 publications
(41 citation statements)
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“…17-Dimethylaminoethylamino-17-demethoxygeldanamycin reduces inflammation in lupus (39), blocks the NF-B inflammatory cascade in immune stimulated macrophages (40) and substantially reduces necrosisinduced cytokine production and permeability increases in a model of endotoxin-induced uveitis (34). Moreover, the synthetic Hsp90 inhibitor EC144 appears to be efficacious in mouse models of endotoxin shock and arthritis (51).…”
Section: Discussionmentioning
confidence: 99%
“…17-Dimethylaminoethylamino-17-demethoxygeldanamycin reduces inflammation in lupus (39), blocks the NF-B inflammatory cascade in immune stimulated macrophages (40) and substantially reduces necrosisinduced cytokine production and permeability increases in a model of endotoxin-induced uveitis (34). Moreover, the synthetic Hsp90 inhibitor EC144 appears to be efficacious in mouse models of endotoxin shock and arthritis (51).…”
Section: Discussionmentioning
confidence: 99%
“…HSP90, a highly conserved and abundant 90 kDa protein, is involved in chaperoning the structures of over 200 client proteins, many of which are involved in growth control as well as mammary tumor cell proliferation [59]. Based on scientific reports, HSP90 may regulate inflammatory events through the modulation of various cytokines and cell signaling pathways [60,61,62]. The efficacy of various HSP90 inhibitors in the treatment of several oncologic diseases, including breast cancer, is currently underway [63,64,65].…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, previous data indicate that HSP90-targeted agents may be helpful for the treatment of inflammatory disease, and that an HSP90 inhibitor can affect multiple signaling processes associated with inflammation (27). Furthermore, inhibition of HSP90 is able to reduce innate immunity responses and diminishes proinflammatory mediator production in immune-stimulated macrophages (28,29). In addition, analysis of inflammatory mediators in crevicular fluid can be used to distinguish peri-implantitis from normal tissue (30).…”
Section: Discussionmentioning
confidence: 99%