Sepsis remains a major cause of morbidity and mortality worldwide. The systemic release of the nuclear protein HMGB1 is a late event in endotoxin-related lethality in mice. The platinating chemotherapeutic Cis induces DNA lesions that sequester HMGB1 within the nucleus of cells. We sought to determine if low, nontoxic doses of Cis could be an effective strategy in ameliorating sepsis-related mortality in a mouse model of CLP. In vitro studies with Cis prevented the LPS-induced release of HMGB1 from RAW264.7 cells, limited MAPK signaling, but had no effect on NF-κB activation or cytokine production. Low, nontoxic doses of Cis decreased mortality following CLP, whether delivered before or after puncture. Protection was associated with a decrease in the systemic release of HMGB1 and protection from end organ injury and in particular, less acute lung injury. Tissue-specific iNOS expression was markedly reduced. Low, nontoxic doses of Cis sequester HMGB1 effectively inside of the nucleus of LPS-stimulated immune cells and prevent its release in response to CLP. Platinating agents in general and Cis specifically may be a novel approach to the treatment of sepsis.
End of preview. The entire article is 8 pages. To view the full-text, please rent this article to continue.
/lp/fed-of-american-socs-for-experimental-biology/low-dose-cisplatin-administration-in-murine-cecal-ligation-and-8XCJNuSA39
Welcome to DeepDyve! Rent Premier Research Articles and Save Up to 90%
Low-dose cisplatin administration in murine cecal ligation and puncture prevents the systemic release of HMGB1 and attenuates lethality
Pan, Pinhua; Cardinal, Jon; Dhupar, Rajeev; Rosengart, Matthew R.; Lotze, Michael T.; Geller, David A.; Billiar, Timothy R.; Tsung, Allan
Follow Journal of Leukocyte Biology
, Volume 86 (3): 625
Fed of American Socs for Experimental Biology – Sep 1, 2009
More Info
More Like This Article
View All dataSource[]=actageo&dataSource[]=aspet&dataSource[]=aaos&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aea&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=ams&dataSource[]=aps_physical&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=apha&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=avs&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=berghahn&dataSource[]=cabi&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=du_press&dataSource[]=esa&dataSource[]=eu_press&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=ejtr&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imanager&dataSource[]=imedpub&dataSource[]=informa_healthcare&dataSource[]=informs&dataSource[]=iop&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=leftcoast&dataSource[]=lu_press&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=nature&dataSource[]=oxford&dataSource[]=pier_professional&dataSource[]=pnas&dataSource[]=portlandpress&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=rcn&dataSource[]=ria&dataSource[]=rsc&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer_journal&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=wiley&dataSource[]=pct
© 2012 DeepDyve, Inc. All rights reserved.
Terms of Service | Privacy Policy
