Peptide compositions that downregulate tlr-4 signaling pathway and methods of producing and using same

Abstract

Compositions that include isolated peptides that inhibit TLR-4 signaling pathways and inflammation are disclosed. Methods of producing and using the compositions to inhibit TLR-4 signaling and/or inflammation are also disclosed herein.

What is claimed is: 
     
         1 . A method of inhibiting TLR4 signaling, the method comprising the step of:
 contacting a cell expressing TLR4 on a surface thereof with a composition wherein the composition binds to TLR4 on the surface of the cell and inhibits TLR4 signaling by the cell, and wherein the composition comprises at least one of:   (a) an isolated peptide fragment of SEQ ID NO:1, wherein the peptide fragment is less than 50 amino acids in length and comprises the amino acid sequence as set forth in SEQ ID NO:3;   (b) an isolated peptide having an amino acid sequence of at least one of SEQ ID NOS:3-7 and 8-246;   (c) an isolated peptide having an amino acid sequence that is at least 90% identical to at least one of SEQ ID NOS:3 and 5; and   (d) an isolated peptide having an amino acid sequence that differs by two amino acids or less from SEQ ID NO:3 or 5.   
     
     
         2 . The method of  claim 1 (a), wherein the isolated peptide fragment comprises a portion of the C-terminal carbohydrate recognition domain of SEQ ID NO:1. 
     
     
         3 . The method of  claim 1 (a), wherein the isolated peptide fragment is less than 40 amino acids in length. 
     
     
         4 . The method of  claim 1 (a), wherein the isolated peptide fragment is less than 30 amino acids in length. 
     
     
         5 . The method of  claim 1 (a), wherein the isolated peptide fragment is less than 25 amino acids in length. 
     
     
         6 . The method of  claim 1 (a), wherein the isolated peptide fragment is 20 amino acids in length. 
     
     
         7 . A method of decreasing the occurrence and/or severity of inflammation associated with a disease condition, the method comprising the step of:
 administering an effective amount of a composition to a subject suffering from or predisposed to the disease condition, thereby decreasing the occurrence and/or severity of inflammation associated with the disease condition in the subject, wherein the composition comprises at least one of:
 (a) an isolated peptide fragment of SEQ ID NO:1, wherein the peptide fragment comprises the motif of SEQ ID NO:2 and is less than 50 amino acids in length; 
 (b) an isolated peptide having an amino acid sequence of at least one of SEQ ID NOS:3-7 and 8-246; 
 (c) an isolated peptide having an amino acid sequence that is at least 90% identical to at least one of SEQ ID NOS:3 and 5; and 
 (d) an isolated peptide having an amino acid sequence that differs by two amino acids or less from SEQ ID NO:3 or 5. 
   
     
     
         8 . The method of  claim 7 , wherein the disease condition is further defined as a disease condition of the lung. 
     
     
         9 . The method of  claim 7 , wherein the disease condition is further defined as an intestinal disease condition having inflammation associated therewith. 
     
     
         10 . The method of  claim 7 , wherein the disease condition is further defined as a cancer. 
     
     
         11 . The method of  claim 7 (a), wherein the isolated peptide fragment comprises a portion of the C-terminal carbohydrate recognition domain of SEQ ID NO:1. 
     
     
         12 . The method of  claim 7 (a), wherein the isolated peptide fragment is less than 40 amino acids in length. 
     
     
         13 . The method of  claim 7 (a), wherein the isolated peptide fragment is less than 30 amino acids in length. 
     
     
         14 . The method of  claim 7 (a), wherein the isolated peptide fragment is less than 25 amino acids in length. 
     
     
         15 . The method of  claim 7 (a), wherein the isolated peptide fragment is 20 amino acids in length. 
     
     
         16 . A method of promoting lung development and/or function in an infant born pre-term, the method comprising the step of:
 administering an effective amount of a composition to the infant, wherein the composition comprises at least one of:
 (a) an isolated peptide fragment of SEQ ID NO:1, wherein the peptide fragment comprises the motif of SEQ ID NO:2 and is less than 50 amino acids in length; 
 (b) an isolated peptide having an amino acid sequence of at least one of SEQ ID NOS:3-7 and 8-246; 
 (c) an isolated peptide having an amino acid sequence that is at least 90% identical to at least one of SEQ ID NOS:3 and 5; and 
 (d) an isolated peptide having an amino acid sequence that differs by two amino acids or less from SEQ ID NO:3 or 5. 
   
     
     
         17 . The method of  claim 16 (a), wherein the isolated peptide fragment comprises a portion of the C-terminal carbohydrate recognition domain of SEQ ID NO:1. 
     
     
         18 . The method of  claim 16 (a), wherein the isolated peptide fragment is less than 40 amino acids in length. 
     
     
         19 . The method of  claim 16 (a), wherein the isolated peptide fragment is less than 30 amino acids in length. 
     
     
         20 . The method of  claim 16 (a), wherein the isolated peptide fragment is less than 25 amino acids in length.