Upregulation of MMP‐9/TIMP‐1 enzymatic system in eosinophilic meningitis caused by Angiostrongylus cantonensis

International Journal of Experimental Pathology - Tập 86 Số 2 - Trang 81-89 - 2005
Kemin Chen1, Hsiu‐Hsiung Lee2, Hui-Lin Chou2, Jer‐Yuh Liu3, Bo‐Cyuan Tsai2, Shih‐Chan Lai2
1Department of Parasitology, Chung Shan Medical University, 110 Section 1, Chien-Kuo North Road, Taichung 402, Taiwan
2Chung Shan Medical University
3Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan

Tóm tắt

Summary

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.

Từ khóa


Tài liệu tham khảo

AlicataJ.E.&JindrakK.(1970) Angiostrongylosis in the Pacific and Southeast Asia. Springfield IL:Thomas.

10.2307/3277651

10.1016/S0002-9440(10)64563-4

10.3109/14756369809035829

Damjanov I., 1996, Histopathology a Color Atlas. and Textbook, 459

Davson H., 1995, Physiology of the CSF and of the Blood‐Brain Barrier, 573

10.4049/jimmunol.156.1.1

Gomez. D.E., 1997, Tissue inhibitors of metalloproteinases: structure, regulation and biological functions, Eur. J. Cell Biol., 74, 111

10.1016/S0021-9258(17)35859-3

10.1093/emboj/cdf676

10.1093/brain/122.8.1579

10.1016/S0165-5728(97)00247-6

10.1093/brain/121.12.2327

10.3201/eid0803.010316

10.1007/BF02821717

Marchi N., 2003, Serum transthyretin monomer as a possible marker of blood‐to‐CSF barrier disruption, J. Neurosci., 23, 1949, 10.1523/JNEUROSCI.23-05-01949.2003

10.1016/S0022-510X(99)00303-2

Nagase H., 1997, Activation mechanism of matrix metalloproteinases, Biol. Chem., 378, 151

10.1074/jbc.274.31.21491

10.1002/(SICI)1097-0215(19960103)65:1<57::AID-IJC10>3.0.CO;2-F

10.1165/ajrcmb.17.4.2877

10.2307/3282627

10.1002/ana.410440404

10.4049/jimmunol.166.6.4223

10.1016/0166-2236(90)90043-A

10.1111/j.1365-3024.1993.tb00619.x

10.1111/j.1365-3024.1988.tb00209.x

10.4049/jimmunol.167.12.7017

10.1172/JCI114867

10.1055/s-2008-1041121

10.1016/0169-4758(94)90124-4

10.1111/j.1365-3024.1988.tb00231.x

Yurchenko P.D., 1990, Molecular architecture of the basement membrane, FASEB J., 4, 1577, 10.1096/fasebj.4.6.2180767