Aminoacyl tRNA synthetases for modulating inflammation
Inflammatory and other cellular response-modulating compositions are provided comprising aminoacyl-tRNA synthetase polypeptides, including active fragments and/or variants thereof. Also provided are methods of using such compositions in the treatment of conditions that benefit from the modulation of inflammation, such as inflammatory diseases or conditions.
1. A method for treating an inflammatory or autoimmune condition in a subject in need thereof, comprising; administering to the subject a composition that comprises a pharmaceutically acceptable carrier and a histidyl-tRNA synthetase (HRS) polypeptide, where the HRS polypeptide comprises the amino acid sequence of SEQ ID NO:28 or a variant thereof that differs from SEQ ID NO:28 by 1-5 amino acids, where the HRS polypeptide has an anti-inflammatory activity and is at least about 90% pure, and where the composition is sterile and pyrogen-free.
2. The method of claim 1 , where the HRS polypeptide is about 509 amino acids in length.
3. The method of claim 2 , where the HRS polypeptide consists essentially of the amino acid sequence of SEQ ID NO:28.
4. The method of claim 1 , where the HRS polypeptide is modified by pegylation.
5. The method of claim 1 , where the HRS polypeptide is a fusion protein that further comprises a heterologous fusion partner.
6. The method of claim 5 , where the HRS polypeptide fusion protein comprises a linker.
7. The method of claim 5 , where the HRS polypeptide fusion protein comprises a heterologous signal peptide.
8. The method of claim 5 , where the heterologous fusion partner comprises an Fc fragment.
9. The method of claim 1 , where the HRS polypeptide is a recombinant polypeptide.
10. The method of claim 1 , where the HRS polypeptide is a synthetic polypeptide.
11. The method of claim 1 , where the composition is formulated with histidine.
12. The method of claim 1 , where the composition comprises a surfactant.
13. The method of claim 1 , where the composition is administered by oral, parenteral, intravenous, intranasal, inhalation, aerosol, intracranial, or intramuscular administration.
14. The method of claim 1 , further comprising administering an anti-inflammatory agent, or immunosuppressive agent.
15. The method of claim 14 , where the anti-inflammatory agent is selected from non-steroidal anti-inflammatory drugs (NSAIDs), immune selective anti-inflammatory derivatives (ImSAIDs), steroids, anti-oxidants, and cytokines.
16. The method of claim 1 , where the inflammatory condition is acute.
17. The method of claim 1 , where the inflammatory condition is chronic.
18. The method of claim 1 , where the inflammatory or autoimmune condition is associated with the vascular system.
19. The method of claim 1 , where the inflammatory or autoimmune condition is associated with the musculoskeletal system.
20. The method of claim 1 , where the inflammatory or autoimmune condition is associated with the respiratory system.
21. The method of claim 1 , where the inflammatory condition or autoimmune is associated with the gastrointestinal system.
22. The method of claim 1 , where the inflammatory condition or autoimmune is associated with the skin.
23. The method of claim 19 , where the inflammatory or autoimmune condition of the musculoskeletal system is selected from auto-immune myositis, Sjogren's syndrome, smooth muscle auto-immune disease, myositis, polymyositis, scleroderma, and chronic muscle inflammation.
24. The method of claim 20 , where the inflammatory or autoimmune condition of the respiratory system is selected from inflammatory lung disease and COPD.
25. The method of claim 21 , where the inflammatory or autoimmune condition of the gastrointestinal system is selected from inflammatory bowel disease (IBD) and colitis.
26. The method of claim 22 , where the inflammatory or autoimmune condition of the skin is selected from irritant dermatitis, allergic contact dermatitis, drug-induced dermatitis, dermatomyositis, pemphigus, and autoimmune dermatitis.
27. A method for treating an inflammatory or autoimmune condition in a subject in need thereof, comprising; a) administering to the subject a composition that comprises a pharmaceutically acceptable carrier and a histidyl-tRNA synthetase (HRS) polypeptide, where the HRS polypeptide comprises the amino acid sequence of SEQ ID NO:28 or a variant thereof that differs from SEQ ID NO:28 by 1-5 amino acids, where the HRS polypeptide has an anti-inflammatory activity and is at least about 90% pure, and where the composition is sterile and pyrogen-free; and b) administering an anti-inflammatory or immunosuppressive therapy.
28. The method of claim 27 , wherein the anti-inflammatory therapy comprises administration of an anti-inflammatory agent selected from a non-steroidal anti-inflammatory drug (NSAIDs), immune selective anti-inflammatory derivatives (ImSAIDs), steroids, anti-oxidants, and cytokines.
29. The method of claim 27 , where the HRS polypeptide is modified by pegylation.
30. The method of claim 27 , where the HRS polypeptide further comprises a heterologous fusion partner.
31. The method of claim 30 , where the HRS polypeptide fusion protein comprises a linker.
32. The method of claim 30 , where the HRS polypeptide fusion protein comprises a heterologous signal peptide.
33. The method of claim 30 , where the heterologous fusion partner comprises an Fc fragment.
34. The method of claim 27 , where the HRS polypeptide is a recombinant polypeptide.
35. The method of claim 27 , where the HRS polypeptide is a synthetic polypeptide.
36. The method of claim 27 , where the composition is formulated with histidine.
37. The method of claim 27 , where the composition comprises a surfactant.
38. The method of claim 27 , where the composition is administered by oral, parenteral, intravenous, intranasal, inhalation, aerosol, intracranial, or intramuscular administration.
39. The method of claim 27 , where the inflammatory condition is acute.
40. The method of claim 27 , where the inflammatory condition is chronic.
41. The method of claim 27 , where the inflammatory or autoimmune condition is associated with the vascular system.
42. The method of claim 27 , where the inflammatory or autoimmune condition is associated with the musculoskeletal system.
43. The method of claim 27 , where the inflammatory or autoimmune condition is associated with the respiratory system.
44. The method of claim 27 , where the inflammatory condition or autoimmune is associated with the gastrointestinal system.
45. The method of claim 27 , where the inflammatory condition or autoimmune is associated with the skin.
46. The method of claim 42 , where the inflammatory or autoimmune condition of the musculoskeletal system is selected from auto-immune myositis, Sjogren's syndrome, smooth muscle auto-immune disease, myositis, polymyositis, scleroderma, and chronic muscle inflammation.
47. The method of claim 43 , where the inflammatory or autoimmune condition of the respiratory system is selected from inflammatory lung disease and COPD.
48. The method of claim 44 , where the inflammatory or autoimmune condition of the gastrointestinal system is selected from inflammatory bowel disease (IBD) and colitis.
49. The method of claim 45 , where the inflammatory or autoimmune condition of the skin is selected from irritant dermatitis, allergic contact dermatitis, drug-induced dermatitis, dermatomyositis, pemphigus, and autoimmune dermatitis.