PROTECTION AGAINST STRESS-MEDIATED DAMAGE FROM IONIZING RADIATION
The use and screening of modulators of apoptosis is disclosed. The modulators may be, for example, modulator of NF-κB activity. The modulators may be used, for example, in the treatment of NF-κB-mediated diseases, conditions, and injuries.
1 . A method of protecting a mammal from a condition that triggers apoptosis comprising administering to a mammal in need thereof a composition comprising an agent that induces NF-kB.
2 . The method of claim 1 wherein the agent is selected from the group consisting of flagellin and TGFβ.
3 . The method of claim 2 wherein the agent is latent TGFβ.
4 . The method of claim 1 wherein the condition is radiation exposure.
5 . The method of claim 2 wherein the composition is administered in combination with a radioprotectant.
6 . The method of claim 5 wherein the radioprotectant is an antioxidant.
7 . The method of claim 6 wherein the antioxidant is selected from the group consisting of amifostine and vitamin E.
8 . The method of claim 5 wherein the radioprotectant is a cytokine.
9 . The method of claim 8 , wherein the cytokine is stem cell factor.
10 . The method of claim 1 wherein the condition is a cancer treatment.
11 . The method of claim 1 wherein the condition is a constitutively active NF-kB cancer.
12 . The method of claim 10 wherein the cancer treatment is chemotherapy or radiation therapy.
13 . The method of claim 10 wherein the composition is administered prior to, together with, or after the treatment.
14 . The method of claim 1 wherein the condition is selected from the group consisting of cell aging, radiation, wounding, poisoning, infection and temperature shock.
15 . A method of screening for a modulator of apoptosis comprising:
(a) adding a suspected modulator to a cell-based apoptosis system;
(b) separately adding a control to a cell-based apoptosis system; and
(c) comparing the level of apoptosis in steps (a) and (b);
wherein the suspected modulator is derived from a mammalian parasite.
16 . The method of claim 15 wherein the modulator of apoptosis is a modulator of NF-kB, wherein the cell-based apoptosis system is a NF-kB-activated expression system, and wherein the level of apoptosis is the level of NF-kB-activated expression.
17 . The method of claim 15 wherein the modulator of apoptosis is a modulator of TGFβ, wherein the cell-based apoptosis system is a TGFβ-activated expression system, and wherein the level of apoptosis is the level of TGFβ-activated expression.
18 . The method of claim 15 wherein the modulator of apoptosis is a modulator of p53, wherein the cell-based apoptosis system is a p53-activated expression system, and wherein the level of apoptosis is the level of p53-activated expression.
19 . The method of claim 15 wherein the parasite is a species selected from the group consisting of Salmonella, Mycoplasma , and Chlamydia.
20 . A modulator identified by the method of claim 19 .