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Drug Repositioning to Alleviate Systemic Inflammatory Response Syndrome Caused by Gram-Negative Bacterial Outer Membrane Vesicles

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Title
Drug Repositioning to Alleviate Systemic Inflammatory Response Syndrome Caused by Gram-Negative Bacterial Outer Membrane Vesicles
Author(s)
Ji Hyun Kim; Jaewook Lee; Kyong-Su Park; Sung-Wook Hong; Yong Song Gho
Subject
drug repositioning, ; extracellular vesicles, ; outer membrane vesicles, ; sepsis, ; systemic inflammatory response syndrome
Publication Date
2018-07
Journal
ADVANCED HEALTHCARE MATERIALS, v.7, no.13, pp.1701476(1) - 1701476(6)
Publisher
WILEY
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://pr.ibs.re.kr/handle/8788114/4958
DOI
10.1002/adhm.201701476
ISSN
2192-2640
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
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