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Elevation of matrix metalloproteinase-9 level in cerebrospinal fluid of tick-borne encephalitis patients is associated with IgG extravassation and disease severity.

Kang X, Li Y, Wei J, Zhang Y, Bian C, Wang K, Wu X, Hu Y, Li J, Yang Y - PLoS ONE (2013)

Bottom Line: Increased concentration of MMP-9 was detected in some of the CSF samples, and the elevation was found to be closely related to CSF TBEV IgG extravasation and enhancement of IL-6 expression.Moreover, elevated levels of MMP-9 were found to be correlated with IL-6 enhancement.In TBE patients, elevated CSF MMP-9 levels were associated with brain inflammatory reaction, disruption of the blood-brain barrier, and disease severity.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

ABSTRACT

Background: Tick-borne encephalitis (TBE), caused by tick-borne encephalitis virus (TBEV), is an infectious disease involving the central nervous system (CNS). The pathogenesis of CNS injury has not been clearly demonstrated. Matrix metalloproteinase-9 (MMP-9) and some cytokines, such as interleukin 6 (IL-6), may play important roles in the disruption of the blood-brain barrier (BBB) and the pathogenesis of TBE.

Methods: 72 cerebrospinal fluid (CSF) samples were collected from TBE patients in north eastern China. IgG levels in CSF and serum were compared and MMP-9 and IL-6 levels were evaluated by ELISA. The correlation between the elevated MMP-9 levels and IgG extravasation, disease severity, and neuroinflammation was analyzed.

Results: Increased concentration of MMP-9 was detected in some of the CSF samples, and the elevation was found to be closely related to CSF TBEV IgG extravasation and enhancement of IL-6 expression. Moreover, elevated levels of MMP-9 were found to be correlated with IL-6 enhancement. Four of the 72 patients, the ones who died, presented with high CSF MMP-9 levels.

Conclusions: In TBE patients, elevated CSF MMP-9 levels were associated with brain inflammatory reaction, disruption of the blood-brain barrier, and disease severity.

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Related in: MedlinePlus

MMP-9 concentrations in TBEV IgG-positive and -negative groups.Diluted MMP-9 standards and CSF samples were added to commercial ELISA plates for MMP-9 detection. After incubation and washing, biotin-conjugated monoclonal antibody was used to bind the MMP-9 in the samples. Horseradish-peroxidase-conjugated avidin was used to amplify the signals. Then a substrate solution capable of reacting with horseradish peroxidase, was added to the wells to produce a color reaction proportional to the amount of MMP-9 present. The MMP-9 concentration in each sample was calculated by comparing it to a MMP-9 standard curve. All of the CSF samples were divided into two groups, TBEV IgG-positive samples and TBEV IgG-negative samples. The difference in the level of MMP-9 expression was analyzed using student t test between the two groups. The limit of detection of this MMP-9 ELISA kit was 1.25 ng/mL.
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pone-0077427-g001: MMP-9 concentrations in TBEV IgG-positive and -negative groups.Diluted MMP-9 standards and CSF samples were added to commercial ELISA plates for MMP-9 detection. After incubation and washing, biotin-conjugated monoclonal antibody was used to bind the MMP-9 in the samples. Horseradish-peroxidase-conjugated avidin was used to amplify the signals. Then a substrate solution capable of reacting with horseradish peroxidase, was added to the wells to produce a color reaction proportional to the amount of MMP-9 present. The MMP-9 concentration in each sample was calculated by comparing it to a MMP-9 standard curve. All of the CSF samples were divided into two groups, TBEV IgG-positive samples and TBEV IgG-negative samples. The difference in the level of MMP-9 expression was analyzed using student t test between the two groups. The limit of detection of this MMP-9 ELISA kit was 1.25 ng/mL.

Mentions: The 72 CSF samples from TBE patients were divided into two groups, a TBEV IgG-positive group and a TBEV IgG-negative group. The concentration of MMP-9 and IL-6 of each sample were analyzed and compared. In the TBEV IgG-positive group, MMP-9 levels of 14 of the 43 samples were below the detection limit. The average MMP-9 level of the remaining 29 samples was 13 ng/ml (1.4–28 ng/ml). However, only one sample in the IgG-negative group (29 samples) showed MMP-9 levels above the detection limit, which was 3 ng/ml. The MMP-9 levels of the other TBEV IgG-negative samples (28 samples) were all below the detection limit. The results are summarized in Table 1 and Figure 1, demonstrating that MMP-9 levels were significantly higher in IgG-positive samples than in IgG-negative samples (P<0.05).


Elevation of matrix metalloproteinase-9 level in cerebrospinal fluid of tick-borne encephalitis patients is associated with IgG extravassation and disease severity.

Kang X, Li Y, Wei J, Zhang Y, Bian C, Wang K, Wu X, Hu Y, Li J, Yang Y - PLoS ONE (2013)

MMP-9 concentrations in TBEV IgG-positive and -negative groups.Diluted MMP-9 standards and CSF samples were added to commercial ELISA plates for MMP-9 detection. After incubation and washing, biotin-conjugated monoclonal antibody was used to bind the MMP-9 in the samples. Horseradish-peroxidase-conjugated avidin was used to amplify the signals. Then a substrate solution capable of reacting with horseradish peroxidase, was added to the wells to produce a color reaction proportional to the amount of MMP-9 present. The MMP-9 concentration in each sample was calculated by comparing it to a MMP-9 standard curve. All of the CSF samples were divided into two groups, TBEV IgG-positive samples and TBEV IgG-negative samples. The difference in the level of MMP-9 expression was analyzed using student t test between the two groups. The limit of detection of this MMP-9 ELISA kit was 1.25 ng/mL.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815297&req=5

pone-0077427-g001: MMP-9 concentrations in TBEV IgG-positive and -negative groups.Diluted MMP-9 standards and CSF samples were added to commercial ELISA plates for MMP-9 detection. After incubation and washing, biotin-conjugated monoclonal antibody was used to bind the MMP-9 in the samples. Horseradish-peroxidase-conjugated avidin was used to amplify the signals. Then a substrate solution capable of reacting with horseradish peroxidase, was added to the wells to produce a color reaction proportional to the amount of MMP-9 present. The MMP-9 concentration in each sample was calculated by comparing it to a MMP-9 standard curve. All of the CSF samples were divided into two groups, TBEV IgG-positive samples and TBEV IgG-negative samples. The difference in the level of MMP-9 expression was analyzed using student t test between the two groups. The limit of detection of this MMP-9 ELISA kit was 1.25 ng/mL.
Mentions: The 72 CSF samples from TBE patients were divided into two groups, a TBEV IgG-positive group and a TBEV IgG-negative group. The concentration of MMP-9 and IL-6 of each sample were analyzed and compared. In the TBEV IgG-positive group, MMP-9 levels of 14 of the 43 samples were below the detection limit. The average MMP-9 level of the remaining 29 samples was 13 ng/ml (1.4–28 ng/ml). However, only one sample in the IgG-negative group (29 samples) showed MMP-9 levels above the detection limit, which was 3 ng/ml. The MMP-9 levels of the other TBEV IgG-negative samples (28 samples) were all below the detection limit. The results are summarized in Table 1 and Figure 1, demonstrating that MMP-9 levels were significantly higher in IgG-positive samples than in IgG-negative samples (P<0.05).

Bottom Line: Increased concentration of MMP-9 was detected in some of the CSF samples, and the elevation was found to be closely related to CSF TBEV IgG extravasation and enhancement of IL-6 expression.Moreover, elevated levels of MMP-9 were found to be correlated with IL-6 enhancement.In TBE patients, elevated CSF MMP-9 levels were associated with brain inflammatory reaction, disruption of the blood-brain barrier, and disease severity.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

ABSTRACT

Background: Tick-borne encephalitis (TBE), caused by tick-borne encephalitis virus (TBEV), is an infectious disease involving the central nervous system (CNS). The pathogenesis of CNS injury has not been clearly demonstrated. Matrix metalloproteinase-9 (MMP-9) and some cytokines, such as interleukin 6 (IL-6), may play important roles in the disruption of the blood-brain barrier (BBB) and the pathogenesis of TBE.

Methods: 72 cerebrospinal fluid (CSF) samples were collected from TBE patients in north eastern China. IgG levels in CSF and serum were compared and MMP-9 and IL-6 levels were evaluated by ELISA. The correlation between the elevated MMP-9 levels and IgG extravasation, disease severity, and neuroinflammation was analyzed.

Results: Increased concentration of MMP-9 was detected in some of the CSF samples, and the elevation was found to be closely related to CSF TBEV IgG extravasation and enhancement of IL-6 expression. Moreover, elevated levels of MMP-9 were found to be correlated with IL-6 enhancement. Four of the 72 patients, the ones who died, presented with high CSF MMP-9 levels.

Conclusions: In TBE patients, elevated CSF MMP-9 levels were associated with brain inflammatory reaction, disruption of the blood-brain barrier, and disease severity.

Show MeSH
Related in: MedlinePlus