Lactoferrin and its immunomodulatory properties

Lactoferrin (LF) is an iron-binding glycoprotein which belongs to a transferrin family. It is available as a commercial extract from bovine milk or colostrum and offers potential as a therapeutic intervention for modulating infections and intestinal pathologies. It was also used a feed supplement for piglets. To date, an ability of LF to bind LPS and then induce cells activation via TLR4 is known. LF itself, however, is belived to be able to activate cells via not yet well described pathway and can induce production of proinflammatory cytokines even without bound LPS. The aim of the study was to bring new information in this field.

In our experiment, porcine monocyte-derived macrophages (MDMF) or Human Embryonic Kidney cell line transfected with hTLR4A-MD2-CD14 (HEK4) were stimulated with purified LPS-free LF or with LF-LPS complex. After six hours, the cells were harvested and a cytokine transcript production was measured by qRT-PCR and the results were confirmed by Western blot analyses.

In MDMF, transcription of proinflammatory cytokines and NFkappaBi molecule were induced even by LPS-free LF. Using HEK4 cell line, it was found that purified LPS-free LF did not induce any proinflammatory response. On the other hand, LF-LPS complex induced strong transcription of proinflammatory cytokines.

Our results suggest that LF is able not only to bind LPS, but LF itself may be a stimulant of proinflammatory response which is different than TLR4-mediated. Supported by the Ministry of Agriculture of the Czech Republic (QJ1310258) and MEYS (project LO1218 under NPU-I program).

Disclosure of Interest: None Declared.