Abstract
Sepsis, also known as systemic inflammatory response syndrome, is a life-threatening condition caused by a pathogenic agent and leading to multiple organ dysfunction syndrome. One of the factors responsible for the excessive intensification of the inflammatory response in the course of inflammation is high-mobility group protein B1 (HMGB1). HMG-1 is a nuclear protein which, after being released to the intercellular space, has a highly pro-inflammatory effect and acts as a late mediator of lethal damage. The purpose of this study was to examine whether the anti-inflammatory action of riboflavin is accompanied by inhibition of HMGB1 release during peritoneal inflammation and zymosan stimulation of macrophages. Peritonitis was induced in male BALB/c and C57BL/6J mice via intraperitoneal injection of zymosan (40 mg/kg). RAW 264.7 macrophages were activated with zymosan (250 µg/ml). Riboflavin (mice, 50 mg/kg; RAW 264.7, 25 µg/ml) was administered 30 min before zymosan, simultaneously with, or 2, 4, 6 h after zymosan. Additionally, mRNA expression of HMGB1 and its intracellular and serum levels were evaluated. The research showed that riboflavin significantly reduces both the expression and the release of HMGB1; however, the effect of riboflavin was time-dependent. The greatest efficacy was found when riboflavin was given 30 min prior to zymosan, and also 2 and 4 h (C57BL/6J; RAW 264.7) or 4 and 6 h (BALB/c) after zymosan. Research showed that riboflavin influences the level of HMGB1 released in the course of inflammation; however, further study is necessary to determine its mechanisms of action.
Highlights
High-mobility group protein B1 (HMGB1) is a member of the HMG protein family that is common in the nucleus of quiescent cells
High-mobility group protein B1 is a protein involved in many biological processes
This study shows that peritoneal administration of zymosan induces high-mobility group protein B1 (HMGB1) release, which is responsible for significant increase in its serum level in the 30th hour of inflammation
Summary
High-mobility group protein B1 (HMGB1) is a member of the HMG protein family that is common in the nucleus of quiescent cells. Recent studies reported that in certain situations HMGB1 may be released from cells to the intercellular space and, acting via various receptors such as RAGE, TLR2, TLR4 or TLR9, induces a pro-inflammatory activation of neutrophils or macrophages (Huang et al 2010; Kim et al 2013). HMGB1 release may occur as a passive leakage from necrotic cells or as an active process of a pro-inflammatory activation of macrophages with endotoxins or pro-inflammatory cytokines (Andersson and Tracey 2011; Youn et al 2011). In the active process HMGB1 is transported to cytoplasm, while release from the cell requires its acetylation, phosphorylation or methylation (Huang et al 2010). The consequence of HMGB1 influence upon immunocompetent cells is the stimulation of releasing inflammatory agents which results in
Sign-in/Register to view highlights & summary 
Published Version (
Free)
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 call