Blockade of Pin1 Prevents Cytokine Production by Activated Immune Cells

Abstract

The invention provides pharmaceutical compositions and methods of treating immunological disorders. The invention also provides pharmaceutical compositions and methods of inducing eosinophil apoptosis, and methods for treating eosinophil-associated disorders comprising inducing eosinophil apoptosis in an individual in need thereof.

1 . A method for treating or preventing an immunological disorder comprising the step of administering to a patient in need thereof an effective amount of a Pin1 inhibitor. 
     
     
         2 . The method of  claim 1 , wherein the Pin1 inhibitor is a dominant negative peptide inhibitor, an antibody, a small molecule inhibitor, antisense oligonucleotide, or a short interfering nucleic acid molecule (siRNA). 
     
     
         3 . The method of  claim 1 , wherein the Pin1 inhibitor is juglone. 
     
     
         4 . The method of  claim 1 , wherein the immunological disorder is an eosinophil-associated disorder. 
     
     
         5 . The method of  claim 4 , wherein the eosinophil-associated disorder is bronchial asthma, eosinophil-associated intranasal inflammation, or eosinophil-associated inflammation of the eye. 
     
     
         6 . The method of  claim 1 , wherein the immunological disorder is asthma. 
     
     
         7 . The method of  claim 1 , wherein the immunological disorder is associated with organ rejection. 
     
     
         8 . The method of  claim 7 , wherein the organ rejection is associated with organ transplantation. 
     
     
         9 . The method of  claim 1 , wherein the Pin1 inhibitor is administered in combination with an immunosuppressive agent for preventing organ or tissue rejection. 
     
     
         10 . The method of  claim 9 , wherein the immunosuppressive agent is Cyclosporin A or FK506, and wherein the Pin1 inhibitor is juglone. 
     
     
         11 . A method for inducing apoptosis in eosinophils comprising the step of contacting an eosinophil with a Pin1 inhibitor. 
     
     
         12 . The method of  claim 11 , wherein the Pin1 inhibitor is a dominant negative peptide inhibitor, an antibody, a small molecule inhibitor, antisense oligonucleotide, or a short interfering nucleic acid molecule (siRNA). 
     
     
         13 . The method of  claim 11 , wherein the Pin1 inhibitor is juglone. 
     
     
         14 . A method of identifying a Pin1 inhibitor, comprising the steps of:
 a. screening one or a plurality of organic compounds that are structurally related to juglone; and   b. determining whether the potential inhibitor inhibits the activity of Pin1.   
     
     
         15 . A method of identifying a compound for treating or preventing an immunological disorder, comprising:
 a. providing a plurality of cells that express Pin1,   b. assaying the cells in the presence and absence of a candidate compound for activity of Pin1; and   c. identifying the compound as a compound for treating an immunological disorder if the Pin1 activity is less in the presence of the candidate compound than in the absence of the candidate compound.