Back to Search
Start Over
Glycolytic inhibitor 2-deoxyglucose suppresses inflammatory response in innate immune cells and experimental staphylococcal endophthalmitis.
- Source :
-
Experimental eye research [Exp Eye Res] 2020 Aug; Vol. 197, pp. 108079. Date of Electronic Publication: 2020 May 23. - Publication Year :
- 2020
-
Abstract
- Previously, we have shown that Staphylococcus (S) aureus induces a glycolytic response in retinal residential (microglia) and infiltrated cells (neutrophils and macrophages) during endophthalmitis. In this study, we sought to investigate the physiological role of glycolysis in bacterial endophthalmitis using a glycolytic inhibitor, 2-deoxyglucose (2DG). Our data showed that 2DG treatment attenuated the inflammatory responses of mouse bone marrow-derived macrophages (BMDM) and neutrophils (BMDN) when challenged with either live or heat-killed S. aureus (HKSA). Among the inflammatory mediators, 2DG caused a significant reduction in levels of cytokines (TNF-α, IL-1β, IL-6) and chemokines (CXCL1 and CXCL2). Western blot analysis of 2DG treated cells showed downregulation of bacterial-induced MEK/ERK pathways. In vivo, intravitreal administration of 2DG both pre- and post-bacterial infection resulted in a significant reduction in intraocular inflammation in C57BL/6 mouse eyes and downregulation of ERK phosphorylation in retinal tissue. Collectively, our study demonstrates that 2DG attenuates inflammatory response in bacterial endophthalmitis and cultured innate immune cells via inhibition of ERK signaling. Thus glycolytic inhibitors in combination with antibiotics could mitigate inflammation-mediated tissue damage in ocular infections.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antimetabolites pharmacology
Blotting, Western
Disease Models, Animal
Endophthalmitis immunology
Endophthalmitis pathology
Enzyme-Linked Immunosorbent Assay
Eye Infections, Bacterial immunology
Eye Infections, Bacterial pathology
Female
Glycolysis drug effects
Male
Mice
Mice, Inbred C57BL
Staphylococcal Infections immunology
Staphylococcal Infections pathology
Deoxyglucose pharmacology
Endophthalmitis drug therapy
Eye Infections, Bacterial drug therapy
Immunity, Innate drug effects
Staphylococcal Infections drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0007
- Volume :
- 197
- Database :
- MEDLINE
- Journal :
- Experimental eye research
- Publication Type :
- Academic Journal
- Accession number :
- 32454039
- Full Text :
- https://doi.org/10.1016/j.exer.2020.108079