Lactoferrin gene expression upregulation in liver during turpentine oil- or bacterial LPS-induced acute phase reaction

Introduction: Lactoferrin (Ltf) is a monomeric glycoprotein which is present in different body fluids including serum. Multifunctional healing abilities of Ltf have been documented in a huge number of publications mainly in the last three decades but no single study has conclusively described the serum sources of this protein particularly during the acute phase reaction (APR). In the current work the role of liver as a source of serum Ltf was investigated during an induced APR.

Methods: Male wild type C57Black6 mice 6–8 weeks old were injected intramuscularly 10ml/kg turpentine oil (TO) or intraperitoneally 50μg of LPS from E.coli. Animals were sacrificed at different time points (from 0h to 24h) after treatment. Liver and sera were collected, and processed for Ltf expression analysis by RT-PCR, western blot, and ELISA. Transferrin was used as an internal control.

Results: Ltf was upregulated at both the mRNA and protein levels in the liver of TO- and LPS-treated mice. The pattern of induction however was different in both animal models indicating distinctive signalling patterns resulting in an acute phase reaction. The increase in hepatic Ltf expression was followed by a rise in serum Ltf levels that were higher after LPS injection than after TO-injection.

Discussion / Conclusion: The iron-transporting protein Ltf is a positive hepatic acute phase protein which probably tries to compensate for transferrin down regulation during an APR. Reactive oxygen intermediates and other free radicals appear during the course of APR¹. Ltf sequesters iron at the site of inflammation and limits the ability of free iron to cause an oxidative stress². Ltf receptors have also been found on monocytes, macrophages, hepatocytes and lymphocytes³. Besides chelating, this protein may thus fulfill a carrier function for iron transport during acute-phase-situations. The current report suggests targeting Ltf for managing oxidative stress during various acute and chronic inflammatory conditions.

Literatur: 1) Koj A. Termination of Acute-Phase Response: Role of Some Cytokines and Anti-Inflammatory Drugs. General Pharmacology 1998; 31 (1):9-18. 2) Guillen C, McInnes IB, Vaughan DM, Kommajosyula S, Van Berkel PH, Leung BP, et al. Enhanced Th1 response to Staphylococcus aureus infection in human lactoferrin-transgenic mice. J Immunol 2002; 168 (8):3950-7. 3) Haversen L, Ohlsson BG, Hahn-Zoric M, Hanson LA, Mattsby-Baltzer I. Lactoferrin down-regulates the LPS-induced cytokine production in monocytic cells via NF-kappa B. Cell Immunol 2002; 220 (2):83-95.

Acute phase reaction - Disease - Inflammation - Injury - Iron - Lactoferrin - Liver - Therapy