Abstract
Proteasome primarily degrades the unneeded or damaged proteins by proteolysis. Disruption of the brain barrier and its resulting meningoencephalitis caused by Angiostrongylus cantonensis are important pathological events in non-permissive hosts. In this study, the results showed upregulated proteasome during A. cantonensis infection. Occludin degradation and matrix metalloproteinase-9 (MMP-9) activity were significantly increased in infected mice than in uninfected mice. Moreover, confocal immunoflourescence microscopy showed that occludin was co-localized with MMP-9. The infected-mice were treated with proteasomal activity inhibitor MG132 by 1.5 and 3.0 mg/kg/day, which resulted in significantly reduced protein levels of phosphorylated IκBα (P<0.05) compared with the untreated control. The phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) showed similar result. In addition, MMP-9 activity and occludin degradation were reduced because of MG132 treatment. These results suggested that the proteasome in A. cantonensis infection degraded phosphorylated IκBα, modulated phosphorylated NF-κB, and then regulated the activation of MMP-9 and occludin degradation. Proteasome alterations were presented in eosinophilic meningitis of BALB/c mice and may contribute to the pathophysiology of eosinophilic meningitis by increasing occludin degradation. This molecule would serve as pivotal regulator in A. cantonensis-induced eosinophilic meningoencephalitis.
Highlights
The rat nematode lungworm Angiostrongylus cantonensis undergoes obligatory intracerebral migration in its hosts and causes cerebral angiostrongyliasis [1]
Our results demonstrated that the proteasome was presented in the cerebrospinal fluid (CSF) and correlated to eosinophilic meningoencephalitis
NF-κB is inferred to have an important role in the induction of pro-inflammatory gene expression and angiostrongyliasis meningitis [6, 25]
Summary
The rat nematode lungworm Angiostrongylus cantonensis undergoes obligatory intracerebral migration in its hosts and causes cerebral angiostrongyliasis [1]. Severe eosinophilic meningitis [2] or meningoencephalitis [3] may result from infection in non-permissive hosts (e.g., human or mice). Matrix metalloproteinase (MMP)-9 activity is closely associated with angiostrongyliasis meningitis [4, 5]. This enzyme is associated with the disruption of the blood-cerebrospinal fluid (CSF) barrier [6] and blood-brain barrier (BBB) [7] in mice with angiostrongyliasis. Proteasome serves as pivotal regulator in angiostrongyliasis meningoencephalitis. The degradation of tight junction protein claudin-5 and dysfunction of the blood-CSF barrier in angiostrongyliasis are mediated by MMP-9 via the IκB-α/NF-κB/ MMP-9 signaling pathway as described in detail previously [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
