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Article

Resolution-Associated Lactoferrin Peptides Limit LPS Signaling and Cytokine Secretion from Human Macrophages

The Laboratory for Molecular Pathways in the Resolution of Inflammation, The Department of Human Biology, University of Haifa, Haifa 3498838, Israel
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(14), 5166; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145166
Received: 12 June 2020 / Revised: 18 July 2020 / Accepted: 19 July 2020 / Published: 21 July 2020
(This article belongs to the Special Issue Peptides for Health Benefits 2020)
The neutrophil granule protein lactoferrin is cleaved and accumulates in efferocytic macrophages as inflammation is resolved. Two peptides present within a resolution-associated 17 kDa fragment of lactoferrin promote the termination of inflammation in vivo by enhancing murine macrophage reprogramming. Here, we report that these two bioactive tripeptides, phenylalanine-lysine-aspartic acid and phenylalanine-lysine-glutamic acid (FKD and FKE, respectively), inhibit ERK and cJun activation following human macrophage exposure to LPS. In addition, these peptides at low concentrations (1–10 μM) modulate human macrophage reprogramming to an anti-inflammatory/pro-resolving phenotype. This was reflected by inhibition of LPS-induced TNF-α and IL-6 secretion and increased IL-10 levels. Moreover, we found naturally occurring FKE analogs (FKECH and FKECHLA) can recapitulate the activity of the short peptide in regulating macrophage cytokine secretion, whereas a reversed EKF peptide was inert in this respect. Curiously, FKD and FKE also regulated cytokine production by bone marrow-derived mouse macrophages, but in a very different fashion than their effect on human macrophages. Thus, lactoferrin peptides limit pro-inflammatory signaling and cytokine production by LPS-activated human macrophages and thereby enhance the resolution of inflammation. View Full-Text
Keywords: resolution of inflammation; lactoferrin; macrophages; LPS; cytokines resolution of inflammation; lactoferrin; macrophages; LPS; cytokines
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MDPI and ACS Style

Lutaty, A.; Soboh, S.; Schif-Zuck, S.; Ariel, A. Resolution-Associated Lactoferrin Peptides Limit LPS Signaling and Cytokine Secretion from Human Macrophages. Int. J. Mol. Sci. 2020, 21, 5166. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145166

AMA Style

Lutaty A, Soboh S, Schif-Zuck S, Ariel A. Resolution-Associated Lactoferrin Peptides Limit LPS Signaling and Cytokine Secretion from Human Macrophages. International Journal of Molecular Sciences. 2020; 21(14):5166. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145166

Chicago/Turabian Style

Lutaty, Aviv, Soaad Soboh, Sagie Schif-Zuck, and Amiram Ariel. 2020. "Resolution-Associated Lactoferrin Peptides Limit LPS Signaling and Cytokine Secretion from Human Macrophages" International Journal of Molecular Sciences 21, no. 14: 5166. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145166

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