title: HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin.
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.
authors.affiliation: Department of Ergonomics and Exercise Physiology, Faculty of Health Science, Jagiellonian University Medical College, Grzegorzecka 20, 31-531, Kraków, Poland. agnieszka.mazur@uj.edu.pl.
authors.forename: Agnieszka Irena
authors.initials: AI
authors.lastname: Mazur-Bialy
authors.affiliation: Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Kraków, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Pocheć
mesh_terms: D000818:Animals; D024243:HMGB1 Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy*; D012256:Riboflavin / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy*; D015054:Zymosan / Q000008:administration & dosage
chemical_list: D024243:HMGB1 Protein; D015054:Zymosan; D012256:Riboflavin
keywords: HMGB1; Inflammation; Macrophages; Peritonitis; Sepsis; Vitamin B2