Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder that can affect nearly every organ in the body. A link has been established between abnormal biotransport of apoptotic cell debris and pathogenesis of SLE [1]. Lupus mice are hyper-responsive to immune stimulation and overproduce inflammatory mediators including IL-6, IL-12, and nitric oxide (NO) [2]. Extracellular expression and transport of inflammatory cytokines are thought to be involved with the inhibited clearance of cellular debris [1]. Hsp90 has a prominent role in folding and conformational regulation of several client proteins, including proteins involved with production of inflammatory mediators [3]. Hsp90 readily binds ATP at the amino (N-) terminal domain. This binding event causes a conformational change in Hsp90 making it “clamp down” on its client protein [3]. Geldanamycin (Geld) is a known inhibitor of Hsp90 that out competes ATP binding at the N-terminal. This prevents chaperone capability and ultimately leads to client protein deactivation, destabilization, and degradation [3]. Hsp90 inhibitors have been shown to suppress immune stimulated release of interleukin 6 (IL-6), IL-12, tumor necrosis factor alpha (TNF-α), and nitric oxide (NO) [4].
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ASME 2010 Summer Bioengineering Conference
June 16–19, 2010
Naples, Florida, USA
Conference Sponsors:
- Bioengineering Division
ISBN:
978-0-7918-4403-8
PROCEEDINGS PAPER
Empirical Modeling the Effect of Hsp90 Inhibition on Cytokines Associated With Impaired Biotransport of Apoptotic Debris
Samuel K. Shimp, III,
Samuel K. Shimp, III
Virginia Polytechnic Institute and State University, Blacksburg, VA
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Christopher M. Reilly,
Christopher M. Reilly
Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, VA
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Marissa Nichole Rylander
Marissa Nichole Rylander
Virginia Polytechnic Institute and State University, Blacksburg, VA
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Samuel K. Shimp, III
Virginia Polytechnic Institute and State University, Blacksburg, VA
Christopher M. Reilly
Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, VA
Marissa Nichole Rylander
Virginia Polytechnic Institute and State University, Blacksburg, VA
Paper No:
SBC2010-19572, pp. 149-150; 2 pages
Published Online:
July 15, 2013
Citation
Shimp, SK, III, Reilly, CM, & Rylander, MN. "Empirical Modeling the Effect of Hsp90 Inhibition on Cytokines Associated With Impaired Biotransport of Apoptotic Debris." Proceedings of the ASME 2010 Summer Bioengineering Conference. ASME 2010 Summer Bioengineering Conference, Parts A and B. Naples, Florida, USA. June 16–19, 2010. pp. 149-150. ASME. https://doi.org/10.1115/SBC2010-19572
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