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10.1016/j.bbadis.2015.08.010 http://scihub22266oqcxt.onion/10.1016/j.bbadis.2015.08.010 C4581992!4581992 !26300484     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26300484 &cmd=llinks): Failed to open stream: HTTP request failed! 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Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction |pdf=|usr=}}{{26300484 }} gab.com Text Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction JO: Biochim Biophys Acta http://www.kidney.de/pget.php?&tw=1&pmid=26300484 #FOAvip Sepsis is an infection-induced severe inflammatory disorder that leads to multiple organ failure. Amongst organs affected, myocardial depression is believed to be a major contributor to septic death. While it has been identified that large amounts of circulating pro-inflammatory cytokines are culprit for triggering cardiac dysfunction in sepsis, the underlying mechanisms remain obscure. Additionally, recent studies have shown that exosomes released from bacteria-infected macrophages are pro-inflammatory. Hence, we examined in this study whether blocking the generation of exosomes would be protective against sepsis-induced inflammatory response and cardiac dysfunction. To this end, we pre-treated RAW264.7 macrophages with GW4869, an inhibitor of exosome biogenesis/release, followed by endotoxin (LPS) challenge. In vivo, we injected wild-type (WT) mice with GW4869 for 1h prior to endotoxin treatment or cecal ligation/puncture (CLP) surgery. We observed that pre-treatment with GW4869 significantly impaired release of both exosomes and pro-inflammatory cytokines (TNF-?, IL-1?, IL-6) in RAW264.7 macrophages. At 12h after LPS treatment or CLP surgery, WT mice pre-treated with GW4869 displayed lower amounts of exosomes and pro-inflammatory cytokines in the serum than control PBS-injected mice. Accordingly, GW4869 treatment diminished the sepsis-induced cardiac inflammation, attenuated myocardial depression and prolonged survival. Together, our findings indicate that blockade of exosome generation in sepsis dampens the sepsis-triggered inflammatory response and thereby, improves cardiac function and survival. Twit Text FOAVip Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction ????Biochim Biophys Acta http://www.kidney.de/pget.php?&tw=1&pmid=26300484 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26300484 #FOAvip English Wikipedia <ref>{{Cite pmid|26300484 }}</ref> Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction #MMPMID26300484 Essandoh K ; Yang L ; Wang X ; Huang W ; Qin D ; Hao J ; Wang Y ; Zingarelli B ; Peng T ; Fan GC Biochim Biophys Acta 2015[Nov]; 1852 (11 ): 2362-71 PMID26300484 show ga Sepsis is an infection-induced severe inflammatory disorder that leads to multiple organ failure. Amongst organs affected, myocardial depression is believed to be a major contributor to septic death. While it has been identified that large amounts of circulating pro-inflammatory cytokines are culprit for triggering cardiac dysfunction in sepsis, the underlying mechanisms remain obscure. Additionally, recent studies have shown that exosomes released from bacteria-infected macrophages are pro-inflammatory. Hence, we examined in this study whether blocking the generation of exosomes would be protective against sepsis-induced inflammatory response and cardiac dysfunction. To this end, we pre-treated RAW264.7 macrophages with GW4869, an inhibitor of exosome biogenesis/release, followed by endotoxin (LPS) challenge. In vivo, we injected wild-type (WT) mice with GW4869 for 1h prior to endotoxin treatment or cecal ligation/puncture (CLP) surgery. We observed that pre-treatment with GW4869 significantly impaired release of both exosomes and pro-inflammatory cytokines (TNF-?, IL-1?, IL-6) in RAW264.7 macrophages. At 12h after LPS treatment or CLP surgery, WT mice pre-treated with GW4869 displayed lower amounts of exosomes and pro-inflammatory cytokines in the serum than control PBS-injected mice. Accordingly, GW4869 treatment diminished the sepsis-induced cardiac inflammation, attenuated myocardial depression and prolonged survival. Together, our findings indicate that blockade of exosome generation in sepsis dampens the sepsis-triggered inflammatory response and thereby, improves cardiac function and survival. äBlockade of exosome generation with GW4869 dampens the sepsis-induced (epmc).pdf DeepDyve Pubget Overpricing