title: LIPOCALIN-2 is a major acute-phase protein in a rat and mouse model of sterile abscess.
abstract: Lipocalin-2 (LCN-2) is a 25-kDa secretory protein currently used as a biomarker for renal injury and inflammation. Its source and cause of the increased serum levels are unclear. The current study compares LCN-2 gene expression with known major acute-phase proteins in the liver in a rat and mouse model of turpentine oil-induced sterile abscess. Serum LCN-2 concentrations increased dramatically up to 200-fold (20 μg/mL) at 48 h after turpentine oil injection. A strong elevation of LCN-2 mRNA in rat liver was observed starting from 4 h up to 48 h after injection, with a maximum (8,738 ± 2,104-fold) at 24 h, which was further confirmed by Western blot analysis. In contrast, the increases in gene expression of α₂-macroglobulin, the major acute-phase protein, and hemoxygenase 1, a positive acute-phase protein, were only 1,025 ± 505-fold and 47 ± 12-fold, respectively, during acute-phase reaction (APR). No considerable change was observed in LCN-2 mRNA in rat kidney and other organs as compared with liver. Using wild-type mice, a massive increase in gene expression of LCN-2, with a maximum of 2,498 ± 84-fold in liver, which is similar to that for serum amyloid A (2,825 ± 233-fold), a major mouse acute-phase protein. However, such an increase was significantly inhibited in interleukin 6 knockout mice during APR. Interleukin 6-treated rat hepatocytes induced a significant time-dependent upregulation of LCN-2.Lipocalin-2 is the major acute-phase protein in rat as compared with α₂-macroglobulin and hemoxygenase 1 and comparable with serum amyloid A in mouse whose gene expression is mainly controlled by interleukin 6. The liver is the main source of serum LCN-2 in the case of APR. ABBREVIATIONS-LCN-2-lipocalin-2-α₂M-α₂-macroglobulin-HO-1-hemoxygenase 1-IL-6-interleukin 6-SAA-serum amyloid A-TO-turpentine oil-APR-acute-phase reaction.
authors.affiliation: Division of Gastroenterology and Endocrinology, University Medical Center Göttingen, Germany.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Sultan
authors.forename: Matteo
authors.initials: M
authors.lastname: Pascucci
authors.forename: Shakil
authors.initials: S
authors.lastname: Ahmad
authors.forename: Ihtzaz Ahmad
authors.initials: IA
authors.lastname: Malik
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianchi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Ramadori
authors.forename: Ghayyor
authors.initials: G
authors.lastname: Ahmad
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ramadori
mesh_terms: D000038:Abscess / Q000378:metabolism*; D000209:Acute-Phase Proteins / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013997:Time Factors; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D015850:Interleukin-6; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D000511:alpha-Macroglobulins; C071332:Lcn2 protein, mouse