PUBLICATION
Glucosamine improves survival in a mouse model of sepsis and attenuates sepsis-induced lung injury and inflammation
- Authors
- Hwang, J.S., Kim, K.H., Park, J., Kim, S.M., Cho, H., Lee, Y., Han, I.O.
- ID
- ZDB-PUB-181127-17
- Date
- 2018
- Source
- The Journal of biological chemistry 294(2): 608-622 (Journal)
- Registered Authors
- Keywords
- O-GlcNAcylation, glucose metabolism, inflammation, lung injury, sepsis
- MeSH Terms
-
- Animals
- Anti-Inflammatory Agents/therapeutic use
- Disease Models, Animal
- Glucosamine/therapeutic use*
- Inflammation/drug therapy*
- Inflammation/etiology*
- Inflammation/pathology
- Lung Injury/drug therapy*
- Lung Injury/etiology*
- Lung Injury/pathology
- Male
- Mice
- Mice, Inbred BALB C
- Neutrophil Infiltration/drug effects
- RAW 264.7 Cells
- Sepsis/complications*
- Sepsis/drug therapy*
- Sepsis/pathology
- Zebrafish
- PubMed
- 30455348 Full text @ J. Biol. Chem.
Citation
Hwang, J.S., Kim, K.H., Park, J., Kim, S.M., Cho, H., Lee, Y., Han, I.O. (2018) Glucosamine improves survival in a mouse model of sepsis and attenuates sepsis-induced lung injury and inflammation. The Journal of biological chemistry. 294(2):608-622.
Abstract
The aim of the current study was to investigate the effects of glucosamine (GlcN) on septic lethality and sepsis-induced inflammation using animal models of mice and zebrafish. GlcN pretreatment improved survival in the cecal ligation and puncture (CLP)-induced sepsis mouse model and attenuated LPS-induced septic lung injury and systemic inflammation. GlcN suppressed LPS-induced M1-specific but not M2-specific gene expression. Furthermore, increased expressions of inflammatory genes in visceral tissue of LPS-injected zebrafish were suppressed by GlcN. GlcN suppressed LPS-induced activation of MAPKs and NF-κB in lung tissue. LPS triggered a reduction in O-GlcNAc levels in nucleocytoplasmic proteins of lung, liver and spleen after 1 day, which returned to normal levels on days 3. GlcN inhibited LPS-induced O-GlcNAc downregulation in mouse lung and visceral tissue of zebrafish. Furthermore, O-GlcNAcase (OGA) level was increased by LPS, which were suppressed by GlcN in mouse and zebrafish. OGA inhibitors suppressed LPS-induced expression of inflammatory genes in RAW264.7 cells and the visceral tissue of zebrafish. Stable knockdown of OGA via shRNA led to increased iNOS expression in response to LPS with or without GlcN in RAW264.7 cells. Overall, our results demonstrate a protective effect of GlcN on sepsis potentially through modulation of O-GlcNAcylation of nucleocytoplasmic proteins.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping