Nf-hev compositions and methods of use
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Abstract
Aspects of the present invention relate to NF-HEV nuclear factor genes and polypeptides. Other aspects related to the use of NF-HEV nuclear factor genes and polypeptides. Other aspects related to the use of NF-HEV nuclear factor polynucleotides and polypeptides expressed in endothelial cells from chronically inflamed tissues, particularly in high endothelial venules endothelial cells (HEVECs) and endothelial cells from HEV-like vessels and small blood vessels, in connection with rheumatoid arthritis and Crohn'"'"'s disease. Aspects of the invention also relates to drug screening assays for identifying compounds capable of modulating NF-HEV activity, wherein such compounds can be used in inhibiting or preventing chronic inflammation.
79 Citations
128 Claims
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1-22. -22. (canceled)
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23. A method of ameliorating symptoms of a condition associated with inflammation, said method comprising:
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identifying a subject having symptoms of a condition associated with inflammation; and
modulating in said subject the level or activity of the NF-HEV polypeptide or a biologically active fragment thereof, thereby ameliorating symptoms of a condition associated with inflammation. - View Dependent Claims (24, 25, 26, 28, 29, 30, 31, 32, 127)
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27. (canceled)
- 33. A method of ameliorating the symptoms of a condition associated with inflammation, said method comprising modulating the level of transcription of at least one promoter responsive to an NF-HEV polypeptide or biologically active fragment thereof.
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38-57. -57. (canceled)
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58. A method of identifying a candidate inhibitor of an NF-HEV polypeptide, said method comprising:
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a) contacting an NF-HEV polypeptide selected from the group consisting of;
a biologically active NF-HEV polypeptide, a polypeptide having at least about 80% amino acid sequence identity to a biologically active NF-HEV polypeptide, and biologically active fragments of either of the foregoing with a test compound; and
b) determining whether said compound selectively binds to said polypeptide, wherein a determination that said compound selectively binds to said polypeptide indicates that said compound is a candidate inhibitor of said polypeptide. - View Dependent Claims (59, 71)
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60. A method of identifying a candidate inhibitor of an NF-HEV polypeptide selected from the group consisting of:
- a biologically active NF-HEV polypeptide, a polypeptide having at least about 80% amino acid sequence identity to a biologically active NF-HEV polypeptide, and biologically active fragments of either of the foregoing, said method comprising;
a) contacting said polypeptide with a test compound; and
b) determining whether said compound selectively inhibits at least one activity of said polypeptide, wherein a determination that said compound selectively inhibits at least one activity of said polypeptide indicates that said compound is a candidate inhibitor of said polypeptide. - View Dependent Claims (61, 65, 66, 67, 68, 69, 70)
- a biologically active NF-HEV polypeptide, a polypeptide having at least about 80% amino acid sequence identity to a biologically active NF-HEV polypeptide, and biologically active fragments of either of the foregoing, said method comprising;
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62. A method of identifying a candidate NF-HEV inhibitor, said method comprising:
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a) providing a cell comprising an NF-HEV polypeptide or a fragment comprising at least 6 consecutive amino acids thereof;
b) contacting said cell with a test compound; and
c) determining whether said compound selectively inhibits at least one NF-HEV activity, wherein a determination that said compound selectively inhibits activity of said polypeptide indicates that said compound is a candidate inhibitor of said polypeptide. - View Dependent Claims (63, 64)
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72-124. -124. (canceled)
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125. A method of identifying a candidate inhibitor of NF-HEV activity, said method comprising:
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(a) providing an NF-HEV polypeptide of SEQ ID NOs;
4-5 or, a fragment comprising a contiguous span of at least 6 contiguous amino acids of a polypeptide according to SEQ ID NOs;
4-5;
(b) providing an NF-HEV target polypeptide or a fragment thereof; and
(c) determining whether a test compound selectively inhibits the ability of said NF-HEV polypeptide to bind to said NF-HEV target polypeptide, wherein a determination that said test compound selectively inhibits the ability of said NF-HEV polypeptide to bind to said NF-HEV target polypeptide indicates that said compound is a candidate inhibitor of NF-HEV activity.
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126. (canceled)
Specification