title: Sustained expression of lipocalin-2 during polymicrobial sepsis.
abstract: Sepsis is a major healthcare problem and a leading cause of death worldwide. There is no dependable diagnosis, and treatment for this condition remains mainly supportive. The etiology of sepsis is related to an overwhelming inflammatory response. In this regard, the antimicrobial protein lipocalin-2 (Lcn2) has been associated with several inflammatory conditions, but its contribution to polymicrobial sepsis is unclear. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP), and Lcn2 mRNA levels and protein expression were measured in liver and lung tissues. We observed that Lcn2 expression was robustly induced in liver and lung of C57BL/6 J (B6) mice, and remained elevated during the stage of innate immune dysfunction observed in sepsis. This response was different in A/J mice, suggesting a contribution of the genetic background, probably due to differences in IL-10 expression between these two mouse strains. Indeed, IL-10 was found to regulate Lcn2 expression in both primary and J774A.1 macrophages. Thus, Lcn2 expression is highly regulated during CLP-induced sepsis, suggesting that this antimicrobial protein could have a role as a potential biomarker for the diagnosis of sepsis.
authors.affiliation: Department of Surgery, University of California San Diego, La Jolla, CA, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Vazquez
authors.affiliation: Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA.
authors.forename: Diego F
authors.initials: DF
authors.lastname: Niño
authors.affiliation: Department of Surgery, University of California San Diego, La Jolla, CA, USA Center for Investigations of Health and Education Disparities, University of California San Diego, La Jolla, CA, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: De Maio
authors.affiliation: Department of Surgery, University of California San Diego, La Jolla, CA, USA dcauvi@ucsd.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Cauvi
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002432:Cecum / Q000293:injuries; D007113:Immunity, Innate / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D008026:Ligation; D000071068:Lipocalin-2; D054834:Lipocalins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D015513:Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018805:Sepsis / Q000235:genetics* / Q000382:microbiology*; D013045:Species Specificity
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D012333:RNA, Messenger; C071332:Lcn2 protein, mouse; D016753:Interleukin-10
keywords: Sepsis; animal model; innate immunity; lipocalin-2; macrophages