Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with meningitis

Abstract

Meningitis is associated with an imbalance between matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of MMP (TIMPs). Serum and CSF were collected prospectively from all patients with meningitis between January 2008 and December 2008 to measure the concentrations of MMP/TIMP in those patients who underwent a lumbar puncture for a presumptive diagnosis of meningitis. A total of 199 patients were enrolled into the study. The concentrations of CSF MMP-9 and TIMP-1 were significantly higher in the meningitis group compared with the control group (p 0.032 and p <0.001, respectively). However, the CSF TIMP-4 levels were significantly lower in the meningitis groups compared with the control groups (p <0.001). Patients with bacterial meningitis had higher CSF MMP-9 and TIMP-1 levels than those who had aseptic meningitis and controls. Patients with various infectious meningitis etiologies tended to have higher CSF MMP-9 expression by gelatin zymography when compared with the controls. In conclusion, MMP/TIMP system dysregulation was found in patients with meningitis, and CSF MMP and TIMP might act as novel indicators in patients with meningitis.

TIMP-1 promotes hypermigration of Toxoplasma-infected primary dendritic cells via CD63–ITGB1–FAK signaling

“…See next page for legend. (Dietmann et al, 2008), and elevated TIMP-1 in cerebrospinal fluid is associated with viral and bacterial meningitis (Kolb et al, 1998;Tsai et al, 2011). Because MMPs can have a role in immunity but can also contribute to immunopathology in bacterial, viral and parasitic infections (Elkington et al, 2005), our data highlight possible pathophysiological effects of TIMP-1: pro-disseminatory effects by activating shuttling leukocytes, while reducing tissue proteolysis (Olafsson et al, 2018) and thereby dampening inflammation systemically or locally in the perivascular microenvironment.…”

Tuberculous meningitis in children is characterized by compartmentalized immune responses and neural excitotoxicity

“…In addition, neutrophil-associated markers, such as S100A8, matrix metalloproteinases (MMP9/19/25) and tissue inhibitor of MMP (TIMP1) were all found to be significantly decreased in TBM. These inflammatory mediators have been found to be highly upregulated in blood or lumbar CSF of TBM 11–13 . In contrast, several pathways associated with glutamate neurotransmitter release, NMDA receptor binding and uptake were positively enriched in TBM (Fig.…”

MMPs and ADAMs in neurological infectious diseases and multiple sclerosis

“…In patients with bacterial meningitis, CSF levels of MMP-1, -3, -7, -8, -9 and -10 have been found to be elevated, whereas CSF levels of MMP-2 remain unaffected [35,[138][139][140][141][142][143]. Similar to animal models, TIMP-1 levels have also been found to be upregulated, whereas TIMP-4 was significantly downregulated compared to control patients [142]. One week after infection, TIMP-1 continues to be highly expressed, whereas MMP-9…”