Chemotactic cytokine III

Abstract

Human chemotactic cytokine III polypeptides and DNA (RNA) encoding such chemotactic cytokines and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such chemotactic cytokines for the treatment of leukemia, tumors, chronic infections, auto-immune disease, fibrotic disorders, wound healing and psoriasis. Antagonists against such chemotactic cytokines and their use as a therapeutic to treat rheumatoid arthritis, auto-immune and chronic and acute inflammatory and infective diseases, allergic reactions, prostaglandin-independent fever, cerebral ischemia, glomerulonephritis, HTLV-1 related diseases and bone marrow failure are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to mutations in the nucleic acid sequences and altered concentrations of the polypeptides. Also disclosed are diagnostic assays for detecting mutations in the polynucleotides encoding chemotactic cytokine III and for detecting altered levels of the polypeptide in a host.

1 . An isolated polynucleotide comprising a polynucleotide having at least 70% identity to a member selected from the group consisting of: 
 (a) a polynucleotide encoding a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:2;    (b) a polynucleotide encoding a polypeptide comprising amino acid 1 to amino acid 53 of SEQ ID NO:2;    (c) a polynucleotide which is complementary to the polynucleotide of (a) or (b); and    (d) a polynucleotide comprising at least 15 bases of the polynucleotide of (a), (b) or (c).    
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA.  
     
     
         3 . The polynucleotide of  claim 1  wherein the polynucleotide is RNA.  
     
     
         4 . The polynucleotide of  claim 2  comprising nucleotide 58 to 371 set forth in SEQ ID NO:1.  
     
     
         5 . The polynucleotide of  claim 2  comprising nucleotide 142 to 370 set forth in SEQ ID NO:1.  
     
     
         6 . The polynucleotide of  claim 2  which encodes a polypeptide comprising amino acid 1 to 53 of SEQ ID NO:2.  
     
     
         7 . An isolated polynucleotide comprising a polynucleotide having at least a 70% identity to a member selected from the group consisting of: 
 (a) a polynucleotide encoding the same mature polypeptide expressed by the human cDNA contained in ATCC Deposit No. 97406;    (b) a polynucleotide complementary to the polynucleotide of (a); and    (c) a polynucleotide comprising at least 15 bases of the polynucleotide of (a) or (b).    
     
     
         8 . A vector comprising the DNA of  claim 2 .  
     
     
         9 . A host cell comprising the vector of  claim 8 .  
     
     
         10 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 9  a polypeptide encoded by said human cDNA.  
     
     
         11 . A process for producing a cell which expresses a polypeptide comprising: transforming or transfecting the cell with the vector of  claim 8 .  
     
     
         12 . A polypeptide comprising an amino acid sequence which is at least 70% identical to a member selected from the group consisting of: 
 (a) a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:2;    (b) a polypeptide comprising amino acid 1 to 53 of SEQ ID NO:2;    (c) a polypeptide comprising at least 15 amino acid residues of the polypeptide of claim (a) or (b).    
     
     
         13 . (canceled)  
     
     
         14 . An agonist to the polypeptide of  claim 12 .  
     
     
         15 . An antibody specific to the polypeptide of  claim 12 .  
     
     
         16 . An antagonist which inhibits the activity of the polypeptide of  claim 12 .  
     
     
         17 . A method for the treatment of a patient having need of CCIII comprising: administering to the patient a therapeutically effective amount of the polypeptide of  claim 12 .  
     
     
         18 . The method of  claim 17  wherein said therapeutically effective amount of the polypeptide is administered by providing to the patient DNA encoding said polypeptide and expressing said polypeptide in vivo.  
     
     
         19 . A method for the treatment of a patient having need to inhibit CCIII polypeptide comprising: administering to the patient a therapeutically effective amount of the antagonist of  claim 16 .  
     
     
         20 . A process for diagnosing a disease or a susceptibility to a disease related to expression of the polypeptide of  claim 12  comprising: 
 determining a mutation in the nucleic acid sequence encoding said polypeptide.    
     
     
         21 . A diagnostic process comprising: 
 analyzing for the presence of the polypeptide of  claim 12  in a sample derived from a host.    
     
     
         22 . A method for identifying compounds which bind to and activate or inhibit a receptor for the polypeptide of  claim 12  comprising: 
 contacting a cell expressing on the surface thereof a receptor for the polypeptide, said receptor being associated with a second component capable of providing a detectable signal in response to the binding of a compound to said receptor, with a compound to be screened under conditions to permit binding to the receptor; and    determining whether the compound binds to and activates or inhibits the receptor by detecting the presence or absence of a signal generated from the interaction of the compound with the receptor.