Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis.

Abstract

Transferrin (Tf) has a major role in T cell activation and proliferation. Here, we investigated whether Tf exerts immunomodulatory effects on T cells and in development of T-cell driven experimental autoimmune encephalomyelitis (EAE). While treatment of concanavalin A-stimulated splenocytes with apotransferrin (ApoTf) did not affect release of IL-1β, TNF, IFN-γ, IL-17, IL-4, and IL-10, it markedly and dose-dependently down-regulated synthesis of IL-2 in these cells. ApoTf also inhibited IL-2 generation in purified CD3+ T cells and the effect was accompanied with down-regulation of MAPK p44/42 and NFκB signaling. Despite impeded IL-2 release, proliferation of splenocytes was not inhibited by ApoTf. Importantly, ApoTf ameliorated EAE in mice and significantly reduced ex vivo IL-2 production in proteolipid protein-specific lymphocytes. Thus ApoTf may be a promising beneficial agent for multiple sclerosis.

• Authors: Tamara Saksida, Djordje Miljkovic, Gordana Timotijevic, Ivana Stojanovic, Sanja Mijatovic, Paolo Fagone, Katia Mangano, Santa Mammana, Claudio Farina, Ester Ascione, Valentina Maiello, Ferdinando Nicoletti, Stanislava Stosic-Grujicic
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 262 Issue 1-2 Pg. 72-8 (Sep 15 2013) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 23890777 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Apoproteins
• Immunosuppressive Agents
• Interleukin-2
• NF-kappa B
• Transferrin
• apotransferrin

Topics

• Animals
• Apoproteins (administration & dosage, physiology)
• Cells, Cultured
• Down-Regulation (immunology)
• Encephalomyelitis, Autoimmune, Experimental (immunology, metabolism, prevention & control)
• Female
• Immunosuppressive Agents (administration & dosage)
• Interleukin-2 (antagonists & inhibitors, biosynthesis)
• MAP Kinase Signaling System (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Mice, Inbred NOD
• NF-kappa B (antagonists & inhibitors)
• Signal Transduction (immunology)
• T-Lymphocytes (cytology, immunology, metabolism)
• Transferrin (administration & dosage, physiology)