title: 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.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ping-Sung
authors.initials: PS
authors.lastname: Chiu
authors.forename: Shih-Chan
authors.initials: SC
authors.lastname: Lai
mesh_terms: D017185:Angiostrongylus cantonensis / Q000276:immunology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000276:immunology / Q000378:metabolism; D062507:Claudin-5 / Q000378:metabolism*; D004151:Dipeptides / Q000008:administration & dosage; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D007976:Leupeptins / Q000008:administration & dosage; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008590:Meningoencephalitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction; D017206:Strongylida Infections / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism
chemical_list: D062507:Claudin-5; D004151:Dipeptides; D007976:Leupeptins; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D016328:NF-kappa B; D020780:Matrix Metalloproteinase 9; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde