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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiostrongylus cantonensis* / immunology
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Animals
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Brain / metabolism
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Brain / parasitology
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Brain / pathology
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Cerebrospinal Fluid / immunology
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Cerebrospinal Fluid / metabolism
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Claudin-5 / metabolism*
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Dipeptides / administration & dosage
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Disease Models, Animal
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Eosinophils / immunology*
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Leupeptins / administration & dosage
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Male
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Matrix Metalloproteinase 9 / metabolism*
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Meningoencephalitis* / drug therapy
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Meningoencephalitis* / immunology
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Meningoencephalitis* / metabolism
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Mice
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Models, Biological
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NF-kappa B / metabolism*
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Proteolysis
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Signal Transduction*
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Strongylida Infections* / drug therapy
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Strongylida Infections* / immunology
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Strongylida Infections* / metabolism
Substances
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Claudin-5
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Dipeptides
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Leupeptins
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N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
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NF-kappa B
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Matrix Metalloproteinase 9
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde
Grants and funding
This study was supported in part by research grant No. NSC 101-2320-B-040-021 from the National Science Council, Republic of China. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.