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Cited 55 time in webofscience Cited 34 time in scopus
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Drug Repositioning to Alleviate Systemic Inflammatory Response Syndrome Caused by Gram-Negative Bacterial Outer Membrane Vesicles SCIE SCOPUS

Title
Drug Repositioning to Alleviate Systemic Inflammatory Response Syndrome Caused by Gram-Negative Bacterial Outer Membrane Vesicles
Authors
Kim, Ji HyunLee, JaewookPark, Kyong-SuHong, Sung-WookGho, Yong Song
Date Issued
2018-07
Publisher
John Wiley and Sons Ltd
Abstract
Sepsis is characterized by systemic inflammatory response syndrome (SIRS) accompanied with infection. Gram-negative bacteria can evoke sepsis by activating the host immune system, such as the release of IL-6 and TNF-alpha, through their virulence factors. Outer membrane vesicles (OMVs), nanosized bilayered proteolipids derived from Gram-negative bacteria, harbor various virulence factors and are shown to induce SIRS. Here, drugs are repositioned to alleviate SIRS caused by Gram-negative bacterial OMVs. Using novel OMV-based drug screening systems, a total of 178 commercially available drugs are primarily screened, and a total of 18 repositioned drug candidates are found to effectively block IL-6 and TNF-alpha production from OMV-stimulated macrophages. After excluding the compounds which are previously known to intervene sepsis or which show cytotoxicity to macrophages, the compounds which show dose-dependency in inhibiting the release of IL-6 and TNF-alpha by the OMV-stimulated macrophages in vitro and which reduce OMV-induced SIRS in vivo are selected. Salbutamol, a beta 2 adrenergic receptor agonist, is selected as a novel candidate to alleviate OMV-induced SIRS. This study sheds light on using Gram-negative bacterial OMVs in exploring novel candidate compounds to alleviate inflammatory diseases including sepsis.
URI
https://oasis.postech.ac.kr/handle/2014.oak/99269
DOI
10.1002/adhm.201701476
ISSN
2192-2640
Article Type
Article
Citation
Advanced healthcare materials, vol. 7, no. 13, 2018-07
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고용송GHO, YONG SONG
Dept of Life Sciences
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