Matrix metalloproteinase-9 leads to claudin-5 degradation via the NF-κB pathway in BALB/c mice with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis.

Abstract

The epithelial barrier regulates the movement of ions, macromolecules, immune cells and pathogens. The objective of this study was to investigate the role of the matrix metalloproteinase (MMP)-9 in the degradation of tight junction protein during infection with rat nematode lungworm Angiostrongylus cantonensis. The results showed that phosphorylation of IκB and NF-κB was increased in mice with eosinophilic meningoencephalitis. Treatment with MG132 reduced the phosphorylation of NF-κB and the activity of MMP-9, indicating upregulation of MMP-9 through the NF-κB signaling pathway. Claudin-5 was reduced in the brain but elevated in the cerebrospinal fluid (CSF), implying that A. cantonensis infection caused tight junction breakdown and led to claudin-5 release into the CSF. Degradation of claudin-5 coincided with alteration of the blood-CSF barrier permeability and treatment with the MMP inhibitor GM6001 attenuated the degradation of claudin-5. These results suggested that degradation of claudin-5 was caused by MMP-9 in angiostrongyliasis meningoencephalitis. Claudin-5 could be used for the pathophysiologic evaluation of the blood-CSF barrier breakdown and tight junction disruption after infection with A. cantonensis.

• Authors: Ping-Sung Chiu, Shih-Chan Lai
• Journal: PloS one (PLoS One) Vol. 8 Issue 3 Pg. e53370 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23505411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Claudin-5
• Dipeptides
• Leupeptins
• N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
• NF-kappa B
• Matrix Metalloproteinase 9
• benzyloxycarbonylleucyl-leucyl-leucine aldehyde

Topics

• Angiostrongylus cantonensis (immunology)
• Animals
• Brain (metabolism, parasitology, pathology)
• Cerebrospinal Fluid (immunology, metabolism)
• Claudin-5 (metabolism)
• Dipeptides (administration & dosage)
• Disease Models, Animal
• Eosinophils (immunology)
• Leupeptins (administration & dosage)
• Male
• Matrix Metalloproteinase 9 (metabolism)
• Meningoencephalitis (drug therapy, immunology, metabolism)
• Mice
• Models, Biological
• NF-kappa B (metabolism)
• Proteolysis
• Signal Transduction
• Strongylida Infections (drug therapy, immunology, metabolism)