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Cited by 441

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction

Open access
Essandoh, Kobina, Yang, Liwang, Wang, Xiaohong, Huang, Wei, Qin, Dongze, Hao, Jiukuan, Wang, Yigang, Zingarelli, Basilia, Peng, Tianqing, Fan, Guo-Chang·2015·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
DOI 10.1016/j.bbadis.2015.08.010
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Abstract

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 1 h 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-α, IL-1β, IL-6) in RAW264.7 macrophages. At 12 h after LPS treatment or CLP surgery, WT mice pretreated 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.

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Metadata

Authors
Essandoh, K., Yang, L., Wang, X., Huang, W., Qin, D., Hao, J., Wang, Y., Zingarelli, B., Peng, T., & Fan, G.-C.
Venue
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher
Elsevier BV
Published
2015-11
Volume
1852
Issue
11
Pages
2362-2371
ISSN
0925-4439 (ISSN-L)
DOI
10.1016/j.bbadis.2015.08.010
OpenAlex
W1141087116
Cited by
441
References
43
FWCI
12.16
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction. https://app.cochat.ai/papers/10.1016/j.bbadis.2015.08.010
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Essandoh, K., Yang, L., Wang, X., Huang, W., Qin, D., Hao, J., Wang, Y., Zingarelli, B., Peng, T., & Fan, G.-C. (2015). Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. https://doi.org/10.1016/j.bbadis.2015.08.010

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