Abstract
Inflammation is a fundamental defensive response to harmful stimuli. However, it can cause damage if it does not subside. To avoid such damage, organisms have developed a mechanism called resolution of inflammation. Here we applied an untargeted metabolomics approach to a sterile and self-resolving animal model of acute inflammation, namely zymosan-induced peritonitis in mice, to examine the effect of inflammation and resolution on the metabolomic profiles. Significant and time-dependent changes in metabolite profiles after zymosan administration were observed in both peritoneal wash fluid (PWF) and plasma. These metabolomic changes correlated well with inflammatory chemokine or cytokine production. In PWF, most of metabolites that could detected increased in zymosan-treated mice, which is suggestive of inflammation, oxidative stress and increased energy demands. In plasma, most metabolites in the central metabolic pathway (glycolysis and TCA cycle) were significantly downregulated after zymosan administration. The concentration of the ketone body 3-hydroxybutyric acid (3-HB) in plasma and PWF increased in zymosan-injected animals indicating upregulation of fatty acid β-oxidation. Increased 3-HB level was observed in the cells that infiltrated into the peritoneal cavity and these infiltrated cells might contribute, at least in part, to the production of 3-HB in the peritoneal cavity.
Highlights
Inflammation is a fundamental defensive response to harmful stimuli, such as pathogens, damaged cells, or irritants
After the administration of low dose of zymosan (1 mg), total cell numbers increased with a maximal infiltration at 6 h [19.262.6610[6] cells] (Figure 1A) and the leukocytes were predominantly composed of polymorphonuclear neutrophils (PMNs), as determined by CD1152 Gr-1+ cells (Figure 1B)
The numbers of total cells and PMNs decreased to control levels on day 7 or day 9 after zymosan administration, which means the inflammation induced by a high dose of zymosan resolved
Summary
Inflammation is a fundamental defensive response to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation will subside normally if harmful stimuli are removed, but it will cause damage to organisms if inflammation dose not subside, which will eventually lead to chronic inflammation [1]. Organisms have developed a mechanism to subside inflammation, namely, resolution of inflammation which is an active process rather than a passive process and mediated by chemical mediators [2]. Among the chemical mediators of resolution are specialized pro-resolving lipid mediators, such as lipoxins, D and E series resolvins, (neuro)protectins, and maresins [3]. Lower dosage of zymosan causes transient inflammation characterized by neutrophil clearance followed by infiltration of resolution-phase macrophages, while higher dosage of zymosan induces more aggressive and prolonged inflammation [5]. Transcriptome of resolution-phase macrophages has been analyzed, the gene that are in the process of resolution of inflammation still remain to be fully clarified [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
