Technology Information

Modulation of TLR-4 Using a MD-2:Endotoxin Complex

A wild-type or mutant MD-2:Endotoxin covalently cross-linked complex can be used to activate or inhibit the TLR-4 receptor, thus modulating an innate immune response.
UIRF Case #:07003


Relevant PublicationsLevel of Development
Technology DescriptionInventor Web Site Link
Patent LinksContact Information
Other Information 

Relevant Publications

Teghanemt A, Prohinar P, Gioannini TL, Weiss JP. Transfer of monomeric endotoxin from MD-2 to CD14: characterization and functional consequences. J Biol Chem. 2007 Dec 14;282(50):36250-6.
Link

Level of Development

General: in vitro

Technology Description

Researchers at the University of Iowa have created a complex that includes a wild-type or mutated protein and endotoxin which serves as a specific modulator of the TLR-4 receptor. This complex consists of an endotoxin, such as lipopolysaccharide (LPS), and the MD-2 protein (wild-type or mutant), the well-characterized co-factor for the TLR-4 receptor. The association of these co-ligands via a covalently cross-linked chimera creates a therapeutic compound that can up- or down-regulate activation of the TLR-4 receptor which serves to increase, decrease or prevent subsequent efforts to activate the host's immune system. Activation of TLR-4 has been associated with release of cytokines, most notably IL-8 and IFN-beta. These cytokines attract other immune cells and prime them to respond to an unknown invader, typically of bacterial origin. Activation of TLR-4 primes the immune system to rapidly respond to newly encountered bacteria and could be used to treat infections, in biodefense, or to increase the efficacy of a given vaccine. Inhibition of this pathway depresses the patients response to TLR-4 activating compounds and prevents the key cytokine-mediated signaling associated with TLR-4 activation and could be used for biodefense or other applications. The MD-2 mutation residues associated with this technology include: 25, 37, 51, 55, 58, 68, 69, 90, 91, 95, 99, 102, 103, 105, 114, 121, 122, 125, 126, 127, 128, 129, 130, 131, 132, 133 and/or 148.

Patent Link(s)

US8137682    

Contact Information

Shannon Sheehan
shannon-sheehan@uiowa.edu
319-335-4605

6 Gilmore Hall, 112 N. Capitol Street, Iowa City, IA 52242     phone: 319-335-4546 fax: 319-335-4486 © University of Iowa 2007. All rights reserved.