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.
Highlights
The rat nematode lungworm Angiostrongylus cantonensis undergoes obligatory intracerebral migration in its hosts and induces the parasitic disease angiostrongyliasis [1]
In an attempt to characterize the mechanisms underlying A. cantonensis-induced blood-cerebrospinal fluid (CSF) barrier dysfunction, we investigated the association of NF-kB, Matrix metalloproteinase (MMP)-9 and claudin-5 in the choroid plexus of the mouse brain after infection with A. cantonensis
Significant elevation of p-IkB-a and p-NF-kB was demonstrated in brain samples from mice with eosinophilic meningoencephalitis caused by infection with A. cantonensis
Summary
The rat nematode lungworm Angiostrongylus cantonensis undergoes obligatory intracerebral migration in its hosts and induces the parasitic disease angiostrongyliasis [1] Infection with this parasite induces severe central nervous system (CNS) disease, especially eosinophilic meningitis [2] or meningoencephalitis [3] in nonpermissive hosts (human or mice). Matrix metalloproteinase (MMP)-9 activity is closely associated with angiostrongyliasis meningitis caused by infection with A. cantonensis [4,5] This enzyme is associated with disruption of the blood-CNS barrier in mice with angiostrongyliasis meningitis and triggers increased cellular infiltration of the subarachnoid space [6]. The CNS can exclude circulating cells and harmful compounds from blood via the blood-brain barrier (BBB) and the blood-CSF barrier, which are formed by tight junction proteins around cerebral epithelial cells of the choroid plexus [7]. Brain microvascular endothelial cells exposed to the human immunodeficiency virus-1
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