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 Hyun; Lee, Jaewook; Park, Kyong-Su; Hong, Sung-Wook; Gho, 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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- There are no files associated with this item.
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