Anti-inflammatory treatment via inhibition of endothelial cell kinesin light chain 1, variant 1 (klc1c)

Abstract

Provided herein are compositions and methods for the inhibition of endothelial cell kinesin light chain 1, variant 1 (KLC1C) expression and/or activity, and treatment or prevention of inflammation therewith.

1 . A method of treating, preventing, or reducing inflammation in a subject comprising administering to the subject an agent that inhibits the binding of kinesin light chain 1, variant 1 (KLC1C) to its cargo. 
     
     
         2 . The method of  claim 1 , wherein administering said agent inhibits transendothelial migration (TEM) of leukocytes. 
     
     
         3 . The method of  claim 1 , wherein administering said agent inhibits targeted recycling of the lateral border recycling compartment (LBRC). 
     
     
         4 . The method of  claim 1 , wherein the agent prevents or reduces the expression of KLC1C. 
     
     
         5 . The method of  claim 4 , wherein the agent is a nucleic acid. 
     
     
         6 . The method of  claim 5 , wherein the agent is an shRNA, siRNA, or antisense oligonucleotide. 
     
     
         7 . The method of  claim 1 , wherein the agent inhibits binding of KLC1C to its cargo. 
     
     
         8 . The method of  claim 7 , wherein the agent is a peptide, antibody, or small molecule. 
     
     
         9 . The method of  claim 7 , wherein the agent is soluble, cell-permeable, and biocompatible. 
     
     
         10 . The method of  claim 1 , further comprising administering a second anti-inflammatory agent to the subject. 
     
     
         11 . The method of  claim 1 , wherein the agent is administered systemically or locally. 
     
     
         12 . The method of  claim 1 , wherein the agent is administered to endothelial or epithelial cells. 
     
     
         13 . The method of  claim 1 , wherein the agent is a peptide, polypeptide, or peptidomimetic that competes with KLC1C for binding to its cargo. 
     
     
         14 . The method of  claim 13 , wherein the agent comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 2. 
     
     
         15 . The method of  claim 13 , wherein the agent comprises an amino acid sequence having at least 80% sequence similarity to SEQ ID NO: 2. 
     
     
         16 . The method of  claim 13 , wherein the agent comprises an amino acid sequence comprising SEQ ID NO: 2. 
     
     
         17 . A pharmaceutical composition comprising a peptide, polypeptide, or peptidomimetic that competes with KLC1C for binding to its cargo. 
     
     
         18 . The method of  claim 17 , wherein the agent comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 2. 
     
     
         19 . The method of  claim 17 , wherein the agent comprises an amino acid sequence having at least 80% sequence similarity to SEQ ID NO: 2. 
     
     
         20 . The method of  claim 17 , wherein the agent comprises an amino acid sequence comprising SEQ ID NO: 2.