Compositions and methods for treating inflammatory diseases
The invention provides compositions and methods for treating inflammatory diseases, such as cardiac or hepatic inflammatory diseases, involving the use of parasite-derived neurotrophic factor (PDNF), or fragment of PDNF. The invention also provides compositions featuring PDNF, or a fragment thereof, and methods for using such compositions for the proliferation and/or mobilization of a stem cell (e.g., cardiac stem cell) or progenitor cell (e.g., hepatic progenitor cell). In one aspect, the invention provides a method of decreasing inflammation in a nonneuronal tissue of a subject. In another aspect, the invention provides a method of decreasing inflammation in a cardiac, liver, pancreas, or gastrointestinal tissue of a subject. In still another aspect, the invention provides a method of increasing expression of an anti-inflammatory factor in a non-neuronal cell or tissue.
1. A method of decreasing inflammation in a non-neuronal tissue of a subject in need thereof, the method comprising: administering to the subject soluble parasite-derived neurotrophic factor (sPDNF) polypeptide of SEQ ID NO: 2, which binds to the TrkA receptor and/or the TrkC receptor on non-neuronal cells or tissue, or a TrkA receptor binding portion of the sPDNF polypeptide selected from residues 1-588 of SEQ ID NO: 2, residues 33-666 of SEQ ID NO: 2, or residues 425-455 of SEQ ID NO: 2, in an amount effective to decrease inflammation in the non-neuronal tissue, wherein the non-neuronal cells or tissue are cardiac or hepatic cells or tissue.
2. The method of claim 1 , wherein the subject has or is at risk of having a cardiac inflammatory disease or a hepatic inflammatory disease.
3. The method of claim 2 , wherein the cardiac inflammatory disease is myocarditis, cardiomyopathy, endocarditis, or pericarditis, and wherein the hepatic inflammatory disease is hepatitis and/or cirrhosis.
4. The method of claim 1 , wherein the subject does not have Chagas disease.
5. A method of treating a cardiac or hepatic inflammatory disease in a subject in need thereof, the method comprising: administering to said subject a therapeutically effective amount of soluble parasite-derived neurotrophic factor (sPDNF) polypeptide as set forth in SEQ ID NO: 2 which binds to the TrkA receptor and/or the TrkC receptor on cardiac or hepatic non-neuronal cells or tissue, or a TrkA receptor binding portion of the sPDNF polypeptide selected from residues 1-588 of SEQ ID NO: 2, residues 33-666 of SEQ ID NO: 2, or residues 425-455 of SEQ ID NO: 2.
6. The method of claim 5 , wherein the cardiac inflammatory disease is myocarditis, cardiomyopathy, endocarditis, or pericarditis, and wherein the hepatic inflammatory disease is hepatitis and/or cirrhosis.
7. The method of claim 5 , wherein the subject does not have Chagas disease.