Z Gastroenterol 2011; 49 - P1_38
DOI: 10.1055/s-0030-1269488

Lipocalin-2 gene expression and production in a model of acute phase response reaction

M Pascucci 1, A Bianchi 2, P Ramadori 3, S Sultan 4, G Martius 4
  • 1III Clinica Medica, Dipartmento di Medicina Clinica, Università degli Studi di Roma “La Sapienza“, Rome, Italien
  • 2Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy, Pavia, Italien
  • 3Geneva University Hospital, Genève 14, Schweiz
  • 4Abt. Gastroenterologie und Endokrinologie, Uniklinikum Göttingen, Göttingen

Lipocalin-2 (LCN-2) is a 25k-Da secretory protein expressed by various tissues, currently used as renal injury marker and recently hypothesized as involved in obesity-related pathologies, as type 2 diabetes mellitus and metabolic syndrome. In the current study a rat model of turpentine oil (TO) induced acute phase reaction (APR) was used to study the pattern of gene expression of LCN-2 in liver and kidney. Serum LCN-2 concentration measured by ELISA test showed a significant increase which reached ≈ 200µg/ml at 48 hours after injection. RT-PCR analysis showed up-regulation of LCN-2 mRNA expression in rat liver starting from 4h and up to 48h after TO injection with a maximum increase of ≈ 8800 folds at 24 hours. Protein expression in rat liver showed an increase of protein concentration starting from 12h after injection. Changes in gene expression of α2 Macroglobulin, major acute phase protein in the rat was also monitored. LCN-2 RNA transcript levels in rat kidney did not show significant increases. Treatment of rat hepatocytes with IL-6 showed an increase of gene expression, along with protein concentration up to 6 hours after treatment. LCN-2 liver gene expression was tested in wild type and IL-6 KO mice treated with intramuscular TO injection. Wild type animals, showed a significant gene up-regulation, with maximum of ≈ 1900 fold increase at 12 hours after injection. IL-6 KO animals showed a reduced elevation with a peak ≈ 37 fold increase at 12h, followed by a fast decrease. LCN-2 gene expression up-regulation and its serum level increase from undetectable levels overcome those of many other positive acute phase proteins. These data and the relationship demonstrated between IL-6 and these changes suggest that LCN-2 can be considered as a main positive acute-phase protein in rat, comparable to C reactive protein (CRP) in human and serum amiloide A (SAA) in mouse. and Further studies should be performed to assess its role in human.

Acute Phase Reaction - Lipocalin-2