Claims
- 1. A method for screening a test compound to determine whether the test compound affects a biological activity of an IL-1 epsilon polypeptide, the method comprising:
a) contacting the test compound and the IL-1 epsilon polypeptide with cells capable of exhibiting the biological activity when contacted with IL-1 epsilon; and, b) analyzing the cells for the occurrence of the biological activity, wherein if the biological activity observed in the presence of the test compound differs from the biological activity that is observed when the test compound is absent, the test compound affects the biological activity of the IL-1 epsilon, and wherein, the IL-1 epsilon polypeptide comprises a polypeptide selected from the group consisting of the polypeptides of SEQ ID NO:6, SEQ ID NO:8, and SEQ ID NO:13, polypeptides encoded by DNAs that hybridize under moderately stringent conditions to the DNAs of SEQ ID NO:5, SEQ ID NO:7, or SEQ ID NO:12 and fragments of the aforesaid polypeptides that exhibit a biological activity of IL-1 epsilon.
- 2. The method of claim 1, wherein the biological activity is selected from the group consisting of:
a) expression of cytokines selected from the group consisting of IL-1 alpha, IL-1 beta, TNF-alpha, IL-10, IFN-gamma, IL-12 p40, IL-6, and combinations thereof; b) expression of cell-surface molecules selected from the group consisting of ICAM-1, TLR4, TLR5, TLR9, DC-B7, and combinations thereof; c) activation of signaling molecules selected from the group consisting of NFkappaB, p38 MAP kinase, Stress-Activated Protein Kinase (SAPK/JNK) and combinations thereof; and d) combinations of the aforesaid activities.
- 3. The method of claim 1, wherein the IL-1 epsilon polypeptides are selected from the group consisting of polypeptides comprising variant amino acid sequence that are at least 80% identical to the polypeptides of SEQ ID NO:6, SEQ ID NO:8, or SEQ ID NO:13.
- 4. The method of claim 2, wherein the IL-1 epsilon polypeptides are selected from the group consisting of polypeptides comprising variant amino acid sequence that are at least 80% identical to the polypeptides of SEQ ID NO:6, SEQ ID NO:8, or SEQ ID NO:13.
- 5. The method of claim 1, wherein the IL-1 epsilon polypeptides are selected from the group consisting of polypeptides comprising the amino acid sequences of SEQ ID NOs:6, 8, or 13 wherein the polypeptides comprise alterations to the amino acid sequences selected from the group consisting of inactivated N-glycosylation site(s), inactivated protease processing site(s), conservative amino acid substitution(s), and combinations thereof.
- 6. The method of claim 2, wherein the IL-1 epsilon polypeptides are selected from the group consisting of polypeptides comprising the amino acid sequences of SEQ ID NOs:6, 8, or 13 wherein the polypeptides comprise alterations to the amino acid sequences selected from the group consisting of inactivated N-glycosylation site(s), inactivated protease processing site(s), conservative amino acid substitution(s), and combinations thereof.
- 7. A combination method for screening a plurality of test compounds to determine whether the test compounds affect a biological activity of an IL-1 epsilon polypeptide, the method comprising:
a) selecting test compounds that affect an ability of IL-1 epsilon to bind an IL-1 epsilon counter structure; b) contacting the selected test compounds and an IL-1 epsilon polypeptide with cells capable of exhibiting a biological activity when contacted with IL-1 epsilon; and c) analyzing the cells for the occurrence of the biological activity, wherein if the biological activity observed in the presence of the selected test compound differs from the biological activity that is observed when the selected test compound is absent, the selected test compound affects the biological activity of the IL-1 epsilon, and wherein, the IL-1 epsilon polypeptide comprises a polypeptide selected from the group consisting of the polypeptides of SEQ ID NO:6, SEQ ID NO:8, and SEQ ID NO:13, polypeptides encoded by DNAs that hybridize under moderately stringent conditions to the DNAs of SEQ ID NO:5, SEQ ID NO:7, or SEQ ID NO:12 and fragments of the aforesaid polypeptides that exhibit a biological activity of IL-1 epsilon.
- 8. The method of claim 7, wherein the biological activity is selected from the group consisting of:
a) expression of cytokines selected from the group consisting of IL-1 alpha, IL-1 beta, TNF-alpha, IL-10, IFN-gamma, IL-12 p40, IL-6, and combinations thereof; b) expression of cell-surface molecules selected from the group consisting of ICAM-1, TLR4, TLR5, TLR9, DC-B7, and combinations thereof; c) activation of signaling molecules selected from the group consisting of NFkappaB, p38 MAP kinase, Stress-Activated Protein Kinase (SAPK/JNK) and combinations thereof; and d) combinations of the aforesaid activities.
- 9. The method of claim 7, wherein the IL-1 epsilon polypeptides are selected from the group consisting of polypeptides comprising variant amino acid sequence that are at least 80% identical to the polypeptides of SEQ ID NO:6, SEQ ID NO:8, or SEQ ID NO:13.
- 10. The method of claim 8, wherein the IL-1 epsilon polypeptides are selected from the group consisting of polypeptides comprising variant amino acid sequence that are at least 80% identical to the polypeptides of SEQ ID NO:6, SEQ ID NO:8, or SEQ ID NO:13.
- 11. The method of claim 7, wherein the IL-1 epsilon polypeptides are selected from the group consisting of polypeptides comprising the amino acid sequences of SEQ ID NOs:6, 8, or 13 wherein the polypeptides comprise alterations to the amino acid sequences selected from the group consisting of inactivated N-glycosylation site(s), inactivated protease processing site(s), conservative amino acid substitution(s), and combinations thereof.
- 12. The method of claim 8, wherein the IL-1 epsilon polypeptides are selected from the group consisting of polypeptides comprising the amino acid sequences of SEQ ID NOs:6, 8, or 13 wherein the polypeptides comprise alterations to the amino acid sequences selected from the group consisting of inactivated N-glycosylation site(s), inactivated protease processing site(s), conservative amino acid substitution(s), and combinations thereof.
- 13. A method of treating an individual afflicted with an inflammatory and/or autoimmune disease comprising administering to the individual an antagonist of IL-1 epsilon selected according to the method of claim 1, wherein the antagonist blocks an inflammatory response selected from the group consisting of rheumatoid arthritis and inflammatory bowel disease.
- 14. The method of claim 13, wherein the inflammatory and/or autoimmune disease is selected from the group consisting of rheumatoid arthritis, inflammatory bowel disease, psoriasis, and combinations thereof.
- 15. The method of claim 13, wherein inflammatory and/or autoimmune disease is selected from the group consisting of: ankylosing spondylitis, Crohn's Disease, ulcerative colitis, psoriatic arthritis, asthma, infection-associated airway hyperactivity, granulomatous lung disease, emphysema, chronic fibrosing alveolitis, acute hyperoxic lung damage, multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, stroke, acute myocardial infarction, unstable angina, arterial restenosis, congestive heart failure, osteoporosis, osteoarthritis, glomerulonephritis, uveitis, Behcet's syndrome, sepsis, acute pancreatitis, diabetes, endometriosis, periodontal disease, heat stroke, glaucoma, multiple myeloma, myeloid leukemia, and combinations thereof.
- 16. A method of treating an individual afflicted with an inflammatory and/or autoirnmune disease comprising administering to the individual an antagonist of IL-1 epsilon selected according to the method of claim 2, wherein the antagonist blocks an inflammatory response selected from the group consisting of rheumatoid arthritis and inflammatory bowel disease.
- 17 The method of claim 16, wherein the inflammatory and/or autoimmune disease is selected from the group consisting of rheumatoid arthritis, inflammatory bowel disease, psoriasis, and combinations thereof.
- 18. The method of claim 16, wherein inflammatory and/or autoimmune disease is selected from the group consisting of: ankylosing spondylitis, Crohn's Disease, ulcerative colitis, psoriatic arthritis, asthma, infection-associated airway hyperactivity, granulomatous lung disease, emphysema, chronic fibrosing alveolitis, acute hyperoxic lung damage, multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, stroke, acute myocardial infarction, unstable angina, arterial restenosis, congestive heart failure, osteoporosis, osteoarthritis, glomerulonephritis, uveitis, Behcet's syndrome, sepsis, acute pancreatitis, diabetes, endometriosis, periodontal disease, heat stroke, glaucoma, multiple myeloma, myeloid leukemia, and combinations thereof.
- 19. A method of treating an individual afflicted with an inflammatory and/or autoimmune disease comprising administering to the individual an antagonist of IL-1 epsilon selected according to the method of claim 3, wherein the antagonist blocks an inflammatory response selected from the group consisting of rheumatoid arthritis and inflammatory bowel disease.
- 20. The method of claim 19, wherein the inflammatory and/or autoimmune disease is selected from the group consisting of rheumatoid arthritis, inflammatory bowel disease, psoriasis, and combinations thereof.
- 21. The method of claim 19, wherein inflammatory and/or autoimmune disease is selected from the group consisting of: ankylosing spondylitis, Crohn's Disease, ulcerative colitis, psoriatic arthritis, asthma, infection-associated airway hyperactivity, granulomatous lung disease, emphysema, chronic fibrosing alveolitis, acute hyperoxic lung damage, multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, stroke, acute myocardial infarction, unstable angina, arterial restenosis, congestive heart failure, osteoporosis, osteoarthritis, glomerulonephritis, uveitis, Behcet's syndrome, sepsis, acute pancreatitis, diabetes, endometriosis, periodontal disease, heat stroke, glaucoma, multiple myeloma, myeloid leukemia, and combinations thereof.
- 22. A method of treating an individual afflicted with an inflammatory and/or autoimmune disease comprising administering to the individual an antagonist of IL-1 epsilon selected according to the method of claim 4, wherein the antagonist blocks an inflammatory response selected from the group consisting of rheumatoid arthritis and inflammatory bowel disease.
- 23. The method of claim 22, wherein the inflammatory and/or autoimmune disease is selected from the group consisting of rheumatoid arthritis, inflammatory bowel disease, psoriasis, and combinations thereof.
- 24. The method of claim 23, wherein inflammatory and/or autoimmune disease is selected from the group consisting of: ankylosing spondylitis, Crohn's Disease, ulcerative colitis, psoriatic arthritis, asthma, infection-associated airway hyperactivity, granulomatous lung disease, emphysema, chronic fibrosing alveolitis, acute hyperoxic lung damage, multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, stroke, acute myocardial infarction, unstable angina, arterial restenosis, congestive heart failure, osteoporosis, osteoarthritis, glomerulonephritis, uveitis, Behcet's syndrome, sepsis, acute pancreatitis, diabetes, endometriosis, periodontal disease, heat stroke, glaucoma, multiple myeloma, myeloid leukemia, and combinations thereof.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation in part of U.S. applications Serial Nos. 60/097,413, 60/098,595, 60/099,974, 09/763,498, (PCT/US99/18771) and No. 60/313,110 filed Aug. 21, 1998, Aug. 31, 1998, Sep. 11, 1998, Aug. 20, 1999, (Aug. 20, 1999) and Aug. 16, 2001, respectively. The entire disclosures of these applications are relied upon and incorporated by reference herein.
Provisional Applications (4)
|
Number |
Date |
Country |
|
60097413 |
Aug 1998 |
US |
|
60098595 |
Aug 1998 |
US |
|
60099974 |
Sep 1998 |
US |
|
60313110 |
Aug 2001 |
US |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
09763498 |
May 2001 |
US |
Child |
09970033 |
Oct 2001 |
US |
Parent |
PCT/US99/18771 |
Aug 1999 |
US |
Child |
09970033 |
Oct 2001 |
US |