Upregulation of MMP-9/TIMP-1 enzymatic system in eosinophilic meningitis caused by Angiostrongylus cantonensis.
Proteolysis depends on the balance between the proteases and their inhibitors. Matrix metalloproteinase-9 (MMP-9) and its specific inhibitors, tissue inhibitors of metalloproteinases (TIMP), contribute to eosinophilic inflammatory reaction in the subarachnoid space of the Angiostrongylus cantonensis-infected mice. The expression of MMP-9 in cerebrospinal fluid (CSF) was significantly increased in mice with eosinophilic meningitis, compared to that in uninfected ones. However, the TIMP-1 levels were unchanged and remained at basal levels at all time points, even in uninfected mice. Elevated MMP-9 mRNA expression coincided with protein levels and proteolytic activity, as demonstrated by means of positive immunoreactivity and gelatin zymography. CSF protein contents correlated significantly with MMP-9 intensity and CSF eosinophilia. In addition, immunohistochemistry demonstrated MMP-9 and TIMP-1 localization in eosinophils and macrophages. When the specific MMP inhibitor, GM6001, was added, MMP-9 enzyme activity was reduced by 45.4%. The percentage of eosinophil increased significantly upon the establishment of infection, but subsided upon inhibition. These results show that MMP-9/TIMP-1 imbalance in angiostrongyliasis may be associated with eosinophilic meningitis.
Chen
Ke-Min
KM
Department of Parasitology, Chung Shan Medical University, 110 Section 1 Chien-Kuo North Road, Taichung 402, Taiwan.
Lee
Hsiu-Hsiung
HH
Chou
Hui-Lin
HL
Liu
Jer-Yuh
JY
Tsai
Bo-Cyuan
BC
Lai
Shih-Chan
SC
D017185:Angiostrongylus cantonensis; D000818:Animals; D015153:Blotting, Western; D020809:Central Nervous System Helminthiasis / Q000134:cerebrospinal fluid* / Q000473:pathology; D004802:Eosinophilia / Q000134:cerebrospinal fluid / Q000469:parasitology / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid* / Q000235:genetics; D008581:Meningitis / Q000134:cerebrospinal fluid* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017206:Strongylida Infections / Q000134:cerebrospinal fluid* / Q000473:pathology; D013346:Subarachnoid Space / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000134:cerebrospinal fluid / Q000235:genetics; D015854:Up-Regulation
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9