Lactoferrin (Lf) is an iron binding glycoprotein of transferrin family, present in almost all mammalian secretions and neutrophils. A variety of biological functions have been ascribed to Lf, including anti-inflammatory and immunomodulatory effects. The protective action of Lf during inflammation is related to its influence on cytokine production and capacity to bind potentially toxic iron at inflammation foci. In our previous studies performed in collaboration with the Department of Clinical Bacteriology, University of Goteborg, we found that LPS (lipopolysaccharide) -induced cytokine production, in particular TNF-a, IL-1β, IL-6, are inhibited by Lf. The binding of protein to LPS could partly explain its inhibitory activity since the effect could be seen when Lf was added before as well after cell stimulation. This suggests that other mechanism(s) than simple LPS scavenging property of Lf is (are) responsible for the inhibitory activity.
In this respect, our group approaches two aspects:
The mode of action of Lf on intracellular signal transduction pathways.
Our preliminary results showed that Lf is taken up by monocytic cells. Therefore it is possible that Lf, following the binding to the cells, might affect some intracellular pathways involved in the cell response to external stimuli such as bacterial endotoxins. LPS stimulation of monocytes has been shown to induce the activation of three subgroups of MAPKinase familly-p38, ERK1/2 and JNK. These enzymes play an important role in the control of proinflammatory cytokine production mediated by LPS. We propose to study the effect of Lf on the phosphorylation and activation of MAPKinases in the presence/absence of LPS. The results will be related to the effect of Lf on the LPS-induced cytokine production in monocytic THP-1 cells. This aspect involves collaboration with Dr. Inger Mattsby-Baltzer group from the Department of Clinical Bacteriology, University of Gothenburg, Sweden.
The anti-inflammatory properties of Lf in vivo: use of liposomes as possible carriers for Lf in the treatment of Rheumatoid Arthritis.
Exhibiting antimicrobial and anti-inflammatory activities Lf could have therapeutic potential in arthritic disease. We are investigating the ability of free and liposome-entrapped Lf to reduce inflammation when administrated to the joint. Current studies aim to establish the suitable liposomal formulation able to deliver Lf efficiently into the joint of mice with collagen-induced rheumatoid arthritis.Liposomes-entrapped Lf is expected to serve as a better tool and therapeutic agent against inflammation. This part is developed in collaboration with Dr. James Brewer group from the Department of Clinical Immunology, Glasgow University, UK, coordinated by Prof. F. Y. Liew.
The project should provide important information for understanding the anti-inflammatory activity of Lf in vivo.
In the next years our research will focus on the cellular and molecular mechanisms involved in the anti-inflammatory and immunomodulatory activities of Lf.
Începând cu data de 16.06.2010, Institutul de Biochimie beneficiază de asistenţă financiară nerambursabilă pentru implementarea proiectului “Întărirea capacităţii administrative”, în baza contractului de finanţare nr. 167/16.06.2010 semnat cu Organismul Intermediar ANCS Bucureşti.