Amino acyl 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 composition, comprising a pharmaceutically-acceptable carrier and an isolated histidyl-tRNA synthetase (HRS) polypeptide selected from (a) a polypeptide that comprises SEQ ID NO:28, (b) a fragment of (a) comprising at least 500 contiguous amino acids of SEQ ID NO:28, and (c) a variant of (a) having at least 95% identity to SEQ ID NO:28, where the HRS polypeptide is not significantly associated with in vivo substances, has an anti-inflammatory activity, reduces the migration of infiltration of immune cells, does not significantly increase the production of pro-inflammatory cytokines, and is at least about 90% pure, and where the composition is sterile and pyrogen-free.
2. The composition of claim 1 , where the HRS polypeptide comprises at least 500 contiguous amino acids of SEQ ID NO:28 and has at least 95% identity to SEQ ID NO:28.
3. The composition of claim 2 , where the HRS polypeptide has at least 98% identity to SEQ ID NO:28.
4. The composition of claim 3 , where the HRS polypeptide comprises SEQ ID NO:28.
5. The composition of claim 1 , where the FIRS polypeptide is about 509 amino acids in length.
6. The composition of claim 5 , where the HRS polypeptide consists essentially of SEQ ID NO:28.
7. The composition of claim 1 , where the FIRS polypeptide is at least about 95% pure.
8. The composition of claim 7 , where the HRS polypeptide is at least about 99% pure.
9. The composition of any of claims 1 - 6 , where the FIRS polypeptide further comprises a heterologous fusion partner.
10. The composition of claim 9 , where the heterologous fusion partner comprises an Fc fragment.
11. The composition of claim 1 , where the FIRS polypeptide is pegylated.
12. The composition of claim 1 , where the HRS polypeptide is a recombinant polypeptide.
13. The composition of claim 12 , where the recombinant polypeptide is produced in a bacterial cell.
14. The composition of claim 12 , where the recombinant polypeptide is produced in a mammalian cell.
15. The composition of claim 1 , where the HRS polypeptide is a synthetic polypeptide.
16. The composition of claim 1 , where the composition is isotonic.
17. The composition of claim 1 , where the composition is a sterile injectable solution.
18. The composition of claim 1 , where the composition is formulated for oral, parenteral, intravenous, intranasal, inhalatory, intracrianial, or intramuscular administration.
19. The composition of claim 1 , where the composition comprises saline.
20. The composition of claim 19 , where the saline comprises PBS.
21. The composition of claim 1 , where the composition comprises a surfactant.
22. The composition of claim 1 , further comprising an anti-inflammatory agent or immunosuppressive agent.
23. The composition of claim 22 , where the agent is selected from non-steroidal anti-inflammatory drugs (NSAIDs), immune-selective anti-inflammatory derivatives (ImSAIDs), steroids, anti-oxidants, and cytokines.