title: Critical role for CCR2 and HMGB1 in induction of experimental endotoxic shock.
abstract: Our aim was to investigate CCR2 and HMGB1 involvement in a murine model of endotoxic shock. We used C57BL/6 CCR2 knockout (KO) mice and wild-type (WT) littermates to establish an optimal dose of LPS. CCR2 KO mice survived more frequently than WT mice after 80, 40 and 20 mg/kg of LPS i.p. Inflammation and redox markers were high in WT mice than in CCR2 KO mice. HMGB1 expression was reduced in CCR2 KO mice in parallel to ERK 1/2 activation. Therefore, we used glycyrrhizic acid (50 mg/kg), an HMGB1 inhibitor in WT mice injected with LPS, and mortality was fully abolished. Thus, drugs targeting CCR2 and HMGB1 could represent future resources for sepsis treatment.
authors.affiliation: Pós-graduação em Biologia Humana e Experimental, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors.forename: Jackson Nogueira
authors.initials: JN
authors.lastname: Alves
authors.forename: Karla Maria Pereira
authors.initials: KM
authors.lastname: Pires
authors.forename: Manuella
authors.initials: M
authors.lastname: Lanzetti
authors.forename: Marina Valente
authors.initials: MV
authors.lastname: Barroso
authors.forename: Cláudia Farias
authors.initials: CF
authors.lastname: Benjamim
authors.forename: Cristiane Aguiar
authors.initials: CA
authors.lastname: Costa
authors.forename: Angela Castro
authors.initials: AC
authors.lastname: Resende
authors.forename: Juliana Carvalho
authors.initials: JC
authors.lastname: Santos
authors.forename: Marcelo Lima
authors.initials: ML
authors.lastname: Ribeiro
authors.forename: Luís Cristóvão
authors.initials: LC
authors.lastname: Porto
authors.forename: Samuel Santos
authors.initials: SS
authors.lastname: Valença
mesh_terms: D000818:Animals; D019695:Glycyrrhizic Acid / Q000008:administration & dosage*; D024243:HMGB1 Protein / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012772:Shock, Septic / Q000139:chemically induced* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015996:Survival Rate
chemical_list: C515335:Ccr2 protein, mouse; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D008070:Lipopolysaccharides; D054390:Receptors, CCR2; D019695:Glycyrrhizic Acid
keywords: CCR2; Glycyrrhizic acid; HMGB1; MCP-1; Sepsis