Abstract: Methods and compositions for modulating neural cell function using antagonists of TLR14 are disclosed. In particular, methods for treating, preventing and/or diagnosing TLR14-associated neurodegenerative conditions and/or disorders are disclosed. Screening methods for evaluating TLR14 modulators, e.g., agonists and antagonists, are also disclosed.

Abstract: Polynucleotides encoding DADD protein are also disclosed, along with vectors, host cells, and methods of making DADD protein. Methods of identifying inhibitors of DADD death domain binding and inhibitors identified by such methods are also disclosed.

Abstract: Novel IL-1-R intracellular ligand proteins are disclosed. Polynucleotides encoding the IL-1-R intracellular ligand protein are also disclosed, along with vectors, host cells, and methods of making the IL-1-R intracellular ligand protein. Pharmaceutical compositions containing the IL-1-R intracellular ligand protein, methods of treating inflammatory conditions, and methods of inhibiting IL-1-R intracellular domain binding are also disclosed. Methods of identifying inhibitors of IL-1-R intracellular domain binding and inhibitors identified by such methods are also disclosed.

Abstract: Novel TNF receptor death domain (“TNF-R1-DD”) ligand proteins are disclosed. Polynucleotides encoding the TNF-R1-DD ligand protein are also disclosed, along with vectors, host cells, and methods of making the TNF-R1-DD ligand protein. Pharmaceutical compositions containing the TNF-R1-DD ligand protein, methods of treating inflammatory conditions, and methods of inhibiting TNF-R death domain binding are also disclosed. Methods of identifying inhibitors of TNF-R death domain binding and inhibitors identified by such methods are also disclosed.

Abstract: The present invention relates to the three dimensional solution structure of the N-terminal domain of TNFR-1 associated death domain protein (“N-TRADD”), as well as the identification and characterization of a C-TRAF2 binding active site of N-TRADD. Also provided for by the present invention are methods of utilizing the three dimensional structures for the design and selection of potent and selective inhibitors of TNF signaling pathways.

Abstract: The present invention provides methods of treating inflammatory diseases/disorders in a subject by inhibiting/antagonizing TREM-1 expression/activity/signal transduction and/or DAP12/TyroBP expression and/or activity. Methods of detecting the presence of inflammatory disease in a subject by detecting TREM-1 and/or DAP12/TyroBP expression and/or activity in the subject or a sample obtained therefrom, wherein increased expression or activity is indicative of the inflammatory disease are also included. The present invention further provides methods for assessing the efficacy of a TREM-1-modulating agent administered to a patient by detecting levels of secreted phosphoprotein 1 (SPP1) and/or one or more other biomarkers in the patient or in a sample from the patient.

Abstract: The invention relates to compositions and methods comprising lymphotoxin-beta receptor (LT?R) modulators, which activate or inhibit LT?R signaling. LT?R modulators are useful for treating lymphocyte mediated immunological diseases and cancer, and more particularly, for regulating mitochondrial-mediated apoptosis. This invention relates to soluble forms of the LT?R complex proteins that act as LT?R activating or inhibiting agents. This invention also relates to the use of soluble molecules, directed against either the LT?R, its ligands, LIGHT and LT?1?2, or its intracellular binding partners, that function to regulate LT?R signaling. A novel screening method for selecting soluble receptors, antibodies and other agents that modulate LT?R signaling is provided.

Abstract: The present invention provides compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5r6, m and n are defined as described herein. The invention also provides methods of making the compounds of formula (I), and methods of treating inflammatory diseases, such as rheumatoid arthritis, in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) to the mammal.

Abstract: The present invention relates to the three dimensional solution structure of receptor interacting protein dead domain (RIP DD), as well as the identification and characterization of various binding active sites of RIP DD. Also provided for by the present invention are methods of utilizing the three dimensional structure for the design and selection of potent and selective inhibitors of TNF signaling pathways.

Abstract: The present invention relates to uses of proteins that bind MK2 to modulate inflammation. More particularly, the invention relates to uses of proteins that bind MK2 for treating condition that are related to inflammation. The invention is useful for treating inflammatory conditions, particularly those in which a decrease in inflammation would be therapeutically beneficial.

Abstract: The invention relates to compositions and methods comprising lymphotoxin-beta receptor (LT?R) modulators, which activate or inhibit LT?R signaling. LT?R modulators are useful for treating lymphocyte mediated immunological diseases and cancer, and more particularly, for regulating mitochondrial-mediated apoptosis. This invention relates to soluble forms of the LT?R complex proteins that act as LT?R activating or inhibiting agents. This invention also relates to the use of soluble molecules, directed against either the LT?R, its ligands, LIGHT and LT?1?2, or its intracellular binding partners, that function to regulate LT?R signaling. A novel screening method for selecting soluble receptors, antibodies and other agents that modulate LT?R signaling is provided.

Abstract: The present invention provides compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, m and n are defined as described herein. The invention also provides methods of making the compounds of formula (I), and methods of treating inflammatory diseases, such as rheumatoid arthritis, in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) to the mammal.

Abstract: The present invention provides compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, m and n are defined as described herein. The invention also provides methods of making the compounds of formula (I), and methods of treating inflammatory diseases, such as rheumatoid arthritis, in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) to the mammal.

Abstract: Novel TNF receptor death domain (“TNF-R1-DD”) ligand proteins are disclosed. Polynucleotides encoding the TNF-R1-DD ligand protein are also disclosed, along with vectors, host cells, and methods of making the TNF-R1-DD ligand protein. Pharmaceutical compositions containing the TNF-R1-DD ligand protein, methods of treating inflammatory conditions, and methods of inhibiting TNF-R death domain binding are also disclosed. Methods of identifying inhibitors of TNF-R death domain binding and inhibitors identified by such methods are also disclosed.

Abstract: Polynucleotides encoding DADD protein are also disclosed, along with vectors, host cells, and methods of making DADD protein. Methods of identifying inhibitors of DADD death domain binding and inhibitors identified by such methods are also disclosed.

Abstract: Novel TNF receptor death domain (“TNF-R1-DD”) ligand proteins are disclosed. Polynucleotides encoding the TNF-R1-DD ligand protein are also disclosed, along with vectors, host cells, and methods of making the TNF-R1-DD ligand protein. Pharmaceutical compositions containing the TNF-R1-DD ligand protein, methods of treating inflammatory conditions, and methods of inhibiting TNF-R death domain binding are also disclosed. Methods of identifying inhibitors of TNF-R death domain binding and inhibitors identified by such methods are also disclosed.

Abstract: The present invention relates to uses of proteins that bind MK2 to modulate inflammation. More particularly, the invention relates to uses of proteins that bind MK2 for treating condition that are related to inflammation. The invention is useful for treating inflammatory conditions, particularly those in which a decrease in inflammation would be therapeutically beneficial.

Abstract: The present invention relates to, among other embodiments, protein complexes which include tumor necrosis factor alpha (TNF-?) and/or tumor necrosis factor alpha receptor (TNFR). Preferably, the complexes comprise at least one polypeptide selected from the group consisting of: NF-?B activating kinase (NAK), RasGAP3, TRCP1, and TRCP2. The present invention further provides assays of identifying a compound for modulating the stability and activity of the complex. Also provided are methods of modulating apoptosis and inflammation, as well as treating TNF-? related diseases.

Abstract: Novel IL-1-R intracellular ligand proteins are disclosed. Polynucleotides encoding the IL-1-R intracellular ligand protein are also disclosed, along with vectors, host cells, and methods of making the IL-1-R intracellular ligand protein. Pharmaceutical compositions containing the IL-1-R intracellular ligand protein, methods of treating inflammatory conditions, and methods of inhibiting IL-1-R intracellular domain binding are also disclosed. Methods of identifying inhibitors of IL-1-R intracellular domain binding and inhibitors identified by such methods are also disclosed.

Abstract: Antibodies to IL-1-R intracellular ligand proteins are disclosed. The antibodies arc useful for inhibiting the binding between IL-1-R and IL-1-R intracellular ligand proteins.