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

Chen, Ke Min; Lee, Hsiu Hsiung; Chou, Hui Lin; Liu, Jer Yuh; Tsai, Bo Cyuan; Lai, Shih‐Chan

doi:10.1111/j.0959-9673.2005.00413.x

Cited by 11 publications

(10 citation statements)

References 28 publications

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“…TIMP-1 is highly inhibitory for MMP-9 [21]. We found a delayed increase of TIMP-1 in SAH patients starting on day 6 indicating an overshoot of MMP activity during the initial phase after SAH [43], [44]. This is the first study that investigates TIMP-1 serum concentrations in SAH patients so far.…”

Section: Discussionmentioning

confidence: 60%

Differential Regulation of Matrix-Metalloproteinases and Their Tissue Inhibitors in Patients with Aneurysmal Subarachnoid Hemorrhage

et al. 2013

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BackgroundMatrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in vascular remodeling, (neuro)inflammation, blood-brain barrier breakdown and neuronal apoptosis. Proinflammatory mechanisms are suggested to play an important role during early brain injury and cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). This study aimed to analyze MMP-3, MMP-9, TIMP-1 and TIMP-3 in patients with SAH and their respective association with cerebral vasospasm (CVS).MethodsBlood samples were collected in 20 SAH patients on days 1 to 7, 9, 11, 13 and 15 and 20 healthy age and gender matched volunteers. Serum MMPs and TIMPs were analyzed using enzyme-linked immunosorbent assay. Doppler sonographic CVS was defined as a mean blood flow velocity above 120 cm/sec in the middle cerebral artery. When discharged from hospital and at 6 month follow-up neurological outcome was evaluated using the Glasgow Outcome Score and the modified Rankin Scale.ResultsMMP-9 was higher in SAH patients compared to healthy controls (p<0.001). Patients with CVS (n = 11) had elevated MMP-9 serum levels compared to patients without CVS (n = 9, p<0.05). Higher MMP-9 was observed in the presence of cerebral ischemia associated with cerebral vasospasm (p<0.05). TIMP-1 was increased in patients with SAH on day 4 (p<0.05). There was an imbalance of the MMP-9/TIMP-1 ratio in favor of MMP-9 in SAH patients, in particular those with CVS (p<0.001). MMP-3 and TIMP-3 were significantly lower in SAH patients throughout day 4 and day 7, respectively (p<0.05). We did not find an association between MMP-, TIMP levels and neurological outcome after 6 months.ConclusionsMMP-3 and -9 are differentially regulated in SAH patients with both enzymes showing peak levels correlating with the development of CVS. The inhibitors TIMP-1 and -3 were low during the acute phase after SAH and increased later on which might suggest a preponderance of pro-inflammatory mechanisms.

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Section: Discussionmentioning

confidence: 60%

Differential Regulation of Matrix-Metalloproteinases and Their Tissue Inhibitors in Patients with Aneurysmal Subarachnoid Hemorrhage

et al. 2013

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“…CNS-resident cells (astrocytes, oligodendrocytes and microglia) [19] may also serve as sources of MMP-9, leading to elevation of CSF levels regardless of pleocytosis. The concentration of MMP-9 in CSF during infections can vary in a time-dependent manner, as has been shown in experimental eosinophilic [20], viral [21] and bacterial [16] meningitis. Previous studies support the idea that MMP-9 levels are considerably higher in children with bacterial than with viral meningitis [10]; so, there might be an indirect link between the type of infectious agent and MMP-9 levels.…”

Section: Discussionmentioning

confidence: 73%

“…CNS‐resident cells (astrocytes, oligodendrocytes and microglia) [19] may also serve as sources of MMP‐9, leading to elevation of CSF levels regardless of pleocytosis. The concentration of MMP‐9 in CSF during infections can vary in a time‐dependent manner, as has been shown in experimental eosinophilic [20], viral [21] and bacterial [16] meningitis.…”

Section: Discussionmentioning

confidence: 99%

Elevated Levels of MMP‐9 and TIMP‐1 in the Cerebrospinal Fluid of Children with Echovirus Type 30 and Mumps Meningitis

Sulik¹,

Wojtkowska

Ołdak³

2008

Scand J Immunol

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Matrix metalloproteinases are involved in leucocyte invasion into the central nervous system (CNS) during meningitis. The aim of the study was to determine whether there are differences in the expression patterns of matrix metalloproteinase‐9 (MMP‐9) and the tissue inhibitor of metalloproteinase‐1 (TIMP‐1) in the cerebrospinal fluid (CSF) of patients with meningitis caused by one of two known distinct viral agents. Concentrations were measured by using an enzyme‐linked immunosorbent assay (ELISA) in 16 children with mumps meningitis, in 25 children with echovirus type 30 meningitis and in a control group of 23 children without any CNS infection. Increased levels of MMP‐9 were found in children with mumps (median 0.48 ng/ml; P < 0.001) and enteroviral meningitis (median 2.76 ng/ml; P < 0.001) compared with that in controls (median: 0.01 ng/ml). Concentrations of TIMP‐1 greatly exceeded concentrations of MMP‐9 and were elevated in children with mumps (median: 56 ng/ml) and echovirus type 30 meningitis (median: 55 ng/ml) compared to controls (median: 17 ng/ml). No significant differences in MMP‐9 or TIMP‐1 levels were detected between the two meningitis groups. The MMP‐9/TIMP‐1 ratio was greater in children with echovirus type 30 than in those with mumps meningitis. There was no correlation between MMP‐9 levels and total CSF cell count. MMP‐9 correlated with CSF absolute neutrophil count in children with echovirus type 30 meningitis (r = 0.431; P < 0.05). The concentration of MMP‐9 is higher in children with viral meningitis, possibly because of infiltrating polymorphonuclear cells present in the initial phase of the disease.

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“…In a study of patients with tuberculosis meningitis, both MMP-2 and MMP-9 were immunolocalized to infiltrating mononuclear cells in the meninges but TIMP-1 and TIMP-2 were expressed in only a small number of inflammatory cells in thickened meninges [11]. However, positive signals for MMP-9 and TIPM-1 were shown to be localized in infiltrating polymorphonuclear cells and mononuclear cells in mice that had eosinophilic meningitis [20].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical analysis of MMP-9, MMP-2 and TIMP-1, TIMP-2 expression in the central nervous system following infection with viral and bacterial meningitis.

Sulik

Chyczewski²

2009

Folia Histochem Cytobiol.

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Matrix metalloproteinases (MMPs) are capable of degrading components of the basal lamina of cerebral vessels, thereby disrupting the blood-brain barrier and inducing leukocyte recruitment. This study provides comprehensive information regarding the cell specificity of matrix metalloproteinases (MMP-2, MMP-9) and their binding tissue inhibitors (TIMP-1, TIMP-2) in the central nervous system during viral and bacterial meningitis. Specifically, we evaluated the immunoreactivity of MMPs and TIMPs in various cell types in brain parenchyma and meninges obtained from autopsy tissues. We found that a higher proportion of endothelial cells were positive for MMP-9 during meningitis when compared to controls. In addition, the immunoreactivity of MMP-9 decreased and the immunoreactivity of TIMP-1 increased in astrocytes upon infection. Furthermore, the results of this study revealed that mononuclear cells were highly immunoreactive for TIMP-1, TIMP-2 and MMP-9 during viral meningitis and that the expression of TIMPs in polymorphonuclear cells was even higher during bacterial meningitis. Taken together the results of this study indicated that the central nervous system resident cells and inflammatory infiltrates contribute to MMPs activity and that the expression patterns vary between cell types and in response to viral and bacterial meningitis.

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

Cited by 11 publications

References 28 publications

Differential Regulation of Matrix-Metalloproteinases and Their Tissue Inhibitors in Patients with Aneurysmal Subarachnoid Hemorrhage

Differential Regulation of Matrix-Metalloproteinases and Their Tissue Inhibitors in Patients with Aneurysmal Subarachnoid Hemorrhage

Elevated Levels of MMP‐9 and TIMP‐1 in the Cerebrospinal Fluid of Children with Echovirus Type 30 and Mumps Meningitis

Immunohistochemical analysis of MMP-9, MMP-2 and TIMP-1, TIMP-2 expression in the central nervous system following infection with viral and bacterial meningitis.

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