14-3-3 Antagonists for the Prevention and Treatment of Arthritis

Abstract

Methods for treating arthritis comprising 14-3-3 antagonists that are capable of specifically binding to extracellularly localized 14-3-3 eta and/or 14-3-3 gamma protein isoforms are provided. In preferred embodiments, the 14-3-3 antagonist is an inhibitory peptide or an anti-14-3-3 antibody. The 14-3-3 antagonists are also formulated in a pharmaceutical compositoin and used in a method for reducing matrix metalloprotease (MMP) expression in the synovial fluid of a patient, wherein the MMP is MMP-1 or MMP-3.

1 - 80 . (canceled) 
     
     
         81 . A method of reducing expression of matrix metalloprotease 1 (MMP-1) in the synovium of a subject, comprising administering to said subject a 14-3-3 eta antibody that specifically binds to an epitope of 14-3-3 eta having an amino acid sequence selected from the group consisting of SEQ ID NOs: 3, 4, 5, 24, 29, 30, 31 and 32. 
     
     
         82 . The method of  claim 81 , wherein said antibody is a monoclonal antibody. 
     
     
         83 . The method of  claim 81 , wherein said monoclonal antibody is a humanized monoclonal antibody. 
     
     
         84 . The method of  claim 81 , wherein said anti-14-3-3 eta antibody discriminates between 14-3-3 protein isoforms. 
     
     
         85 . The method of  claims 81 , wherein said anti-14-3-3 eta antibody specifically binds to a peptide consisting of the amino acid sequence NSVVEASEAAYK (SEQ ID NO: 3) or NSVVEASEA (SEQ ID NO: 4). 
     
     
         86 . The method of  claim 81 , wherein said anti-14-3-3 eta antibody specifically binds to a peptide consisting of the amino acid sequence LDKFLIKNSNDF (SEQ ID NO:30). 
     
     
         87 . The method of  claim 81 , wherein said anti-14-3-3 eta antibody is specifically binds to a peptide consisting of the amino acid sequence KKLEKVKAYR (SEQ ID NO:31). 
     
     
         88 . The method of  claim 81 , wherein said anti-14-3-3 eta antibody specifically binds to a peptide consisting of the amino acid sequence KNSWEASEAAYKEA (SEQ ID NO:32). 
     
     
         89 . The method of  claim 81 , wherein said anti-14-3-3 eta antibody specifically binds to a peptide consisting of the amino acid sequence KKNSVVEASEAAYKEAF (SEQ ID NO:24). 
     
     
         90 . The method of  claim 81 , wherein said anti-14-3-3 eta antibody specifically binds to a peptide consisting of the amino acid sequence VEASEAAYK (SEQ ID NO:5). 
     
     
         91 . The method of  claim 81 , wherein said antibody is produced by a hybridoma selected from the group consisting of AUG3-CKNS-2D5, AUG3-CKNS-7F8, AUG3-CKNS-7H8, and AUG4-ETA-8F10.