Flagellin related polypeptides and uses thereof
The use of flagellin and flagellin related polypectides for the protection of mammals from the effects of apoptsis is described.
1. A method of treating apoptosis-mediated tissue damage in a mammal comprising administering to a mammal in need thereof a composition comprising a flagellin polypeptide, wherein the polypeptide comprises an amino terminal domain comprising amino acids 1-163 of SEQ ID NO: 1 and a carboxyl terminal domain comprising amino acids 402-450 of SEQ ID NO: 1, wherein the amino terminal and the carboxyl terminal domains are linked by a polypeptide linker that does not comprise amino acids 177-401 of SEQ ID NO: 1, and wherein the apoptosis is attributable to a cellular stress.
2. The method of claim 1 , wherein the carboxyl terminal domain comprises amino acids 402-505 of SEQ ID NO: 1.
3. The method of claim 1 , wherein the amino terminal domain comprises amino acids 1-176 of SEQ ID NO: 1.
4. The method of claim 1 , wherein the polypeptide linker comprises the E. coli hinge region (ECH) of E. coli MukB protein.
5. The method of claim 1 , wherein the polypeptide linker comprises a sequence selected from the group consisting of SEQ ID NOs: 3 and 4.
6. The method of claim 1 , wherein the flagellin comprises SEQ ID NO: 8.
7. The method of claim 1 , wherein the cellular stress is due to radiation, and wherein the composition is administered in combination with a radioprotectant.
8. The method of claim 7 , wherein the radioprotectant is an antioxidant.
9. The method of claim 8 , wherein the antioxidant is selected from the group consisting of amifostine and vitamin E.
10. The method of claim 7 , wherein the radioprotectant is a cytokine.
11. The method of claim 10 , wherein the cytokine is a stem cell factor.
12. The method of claim 7 , wherein the radioprotectant is a growth factor.
13. The method of claim 12 , wherein the growth factor is keratinocyte growth factor.
14. The method of claim 7 , wherein the radioprotectant is a steroid.
15. The method of claim 14 , wherein the steroid is 5-androstenediol.
16. The method of claim 7 , wherein the radioprotectant is ammonium trichloro(dioxoethylene-O,O′)tellurate.
17. The method of claim 1 , wherein the mammal is a human.
18. The method of claim 1 , wherein the radiation is cancer radiotherapy.
19. The method of claim 1 , wherein the composition is administered prior to, together with, or after radiation.