HSP90 inhibition suppresses lipopolysaccharide-induced lung inflammation in vivo.
HSP90 inhibition suppresses lipopolysaccharide-induced lung inflammation in vivo.
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DOI：
10.1371/journal.pone.0114975
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Anderson GP
中科院分区：
文献类型：
--
作者：
Lilja A;Weeden CE;McArthur K;Nguyen T;Donald A;Wong ZX;Dousha L;Bozinovski S;Vlahos R;Burns CJ;Asselin-Labat ML;Anderson GP
Inflammation is an important component of cancer diathesis and treatment-refractory inflammation is a feature of many chronic degenerative lung diseases. HSP90 is a 90kDa protein which functions as an ATP-dependent molecular chaperone that regulates the signalling conformation and expression of multiple protein client proteins especially oncogenic mediators. HSP90 inhibitors are in clinical development as cancer therapies but the myeleosuppressive and neutropenic effect of first generation geldanamycin-class inhibitors has confounded studies on the effects on HSP90 inhibitors on inflammation. To address this we assessed the ability of Ganetespib, a non-geldanamycin HSP90 blocker, to suppress lipopolysaccharide (LPS)-induced cellular infiltrates, proteases and inflammatory mediator and transcriptional profiles. Ganetespib (10–100mg/kg, i.v.) did not directly cause myelosuppression, as assessed by video micrography and basal blood cell count, but it strongly and dose-dependently suppressed LPS-induced neutrophil mobilization into blood and neutrophil- and mononuclear cell-rich steroid-refractory lung inflammation. Ganetespib also suppressed B cell and NK cell accumulation, inflammatory cytokine and chemokine induction and MMP9 levels. These data identify non-myelosuppresssive HSP90 inhibitors as potential therapies for inflammatory diseases refractory to conventional therapy, in particular those of the lung.
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影响因子：
4.8
作者：
Liu, Kenneth;Gualano, Rosa C.;Bozinovski, Steven
通讯作者：
Bozinovski, Steven
影响因子：
3
作者：
Iyer, Gopa;Morris, Michael J.;Rathkopf, Dana;Slovin, Susan F.;Steers, Macaulay;Larson, Steven M.;Schwartz, Lawrence H.;Curley, Tracy;DeLaCruz, Anthony;Ye, Qing;Heller, Glenn;Egorin, Merrill J.;Ivy, S. Percy;Rosen, Neal;Scher, Howard I.;Solit, David B.
通讯作者：
Solit, David B.
影响因子：
3.7
作者：
Proia DA;Foley KP;Korbut T;Sang J;Smith D;Bates RC;Liu Y;Rosenberg AF;Zhou D;Koya K;Barsoum J;Blackman RK
通讯作者：
Blackman RK
DOI：
10.1152/ajplung.00275.2003
发表时间：
2004-04-01
影响因子：
4.9
作者：
Bozinovski, S;Jones, J;Anderson, GP
通讯作者：
Anderson, GP
影响因子：
5.7
作者：
Acquaviva, Jaime;Smith, Donald L.;Proia, David A.
通讯作者：
Proia, David A.