Molecular signaling blockade as a new approach to inhibit leukocyte-endothelial interactions for inflammatory bowel disease treatment

Cell Adh Migr. 2009 Jul-Sep;3(3):296-9. doi: 10.4161/cam.3.3.9152. Epub 2009 Jul 2.

Abstract

Mitogen-activated protein kinases (MAPK) are among the major widespread transduction pathways in humans. They are involved in several inflammatory disorders, including the pathogenesis of inflammatory bowel disease (IBD). A recent paper showed that activated MAPK are upregulated on endothelium and fibroblasts from intestinal biopsies of active IBD patients. In vitro experiments demonstrated that MAPK activation on intestinal endothelial cells and fibroblasts are responsible for the production of certain chemokines, increased leukocyte adhesion and transmigration. Specific local inhibition of MAPK activity on endothelial cells and fibroblasts may provide a new mechanism to control mucosal inflammation and leukocyte recruitment into the intestine of active IBD patients.

MeSH terms

  • Cell Communication* / drug effects
  • Chemotaxis / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / enzymology
  • Endothelial Cells / pathology*
  • Enzyme Activation / drug effects
  • Humans
  • Inflammatory Bowel Diseases / enzymology
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / therapy*
  • Leukocytes / drug effects
  • Leukocytes / enzymology
  • Leukocytes / pathology*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Models, Biological
  • Protein Kinase Inhibitors / pharmacology
  • Signal Transduction* / drug effects

Substances

  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinases