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Updated: Mar 7, 2026
Detection of Functional Matrix Metalloproteinases by Zymography
Published on: November 8, 2010
Involvement of matrix metalloproteinases in chronic Q fever
A F M Jansen1, T Schoffelen1, J Textoris2
1Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands; Radboud Expert Centre for Q fever and Radboud Centre for Infectious Diseases (RCI), Radboud University Medical Centre, The Netherlands.
Objectives:
Chronic Q fever is a persistent infection with the intracellular Gram-negative bacterium Coxiella burnetii, which can lead to complications of infected aneurysms. Matrix metalloproteinases (MMPs) cleave extracellular matrix and are involved in infections as well as aneurysms. We aimed to study the role of MMPs in the pathogenesis of chronic Q fever.
Methods:
We investigated gene expression of MMPs through microarray analysis and MMP production with ELISA in C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients with chronic Q fever and healthy controls. Twenty single nucleotide polymorphisms (SNPs) of MMP and tissue inhibitor of MMP genes were genotyped in 139 patients with chronic Q fever and 220 controls with similar cardiovascular co-morbidity. Additionally, circulating MMPs levels in patients with chronic Q fever were compared with those in cardiovascular controls with and without a history of past Q fever.
Results:
In healthy controls, the MMP pathway involving four genes (MMP1, MMP7, MMP10, MMP19) was significantly up-regulated in C. burnetii-stimulated but not in Escherichia coli lipopolysaccharide -stimulated PBMCs. Coxiella burnetii induced MMP-1 and MMP-9 production in PBMCs of healthy individuals (both p<0.001), individuals with past Q fever (p<0.05, p<0.01, respectively) and of patients with chronic Q fever (both p<0.001). SNPs in MMP7 (rs11568810) (p<0.05) and MMP9 (rs17576) (p<0.05) were more common in patients with chronic Q fever. Circulating MMP-7 serum levels were higher in patients with chronic Q fever (median 33.5 ng/mL, interquartile range 22.3-45.7 ng/mL) than controls (20.6 ng/mL, 15.9-33.8 ng/mL).
Conclusion:
Coxiella burnetii-induced MMP production may contribute to the development of chronic Q fever.
Insights
Matrix metalloproteinases (MMPs) are implicated in chronic Q fever pathogenesis. Coxiella burnetii infection stimulates MMP production, suggesting a role in disease development.
Area of Science:
- Infectious Diseases
- Immunology
- Genetics
Background:
- Chronic Q fever is a persistent Coxiella burnetii infection.
- Complications include infected aneurysms.
- Matrix metalloproteinases (MMPs) are involved in infection and aneurysm pathogenesis.
Purpose of the Study:
- To investigate the role of MMPs in chronic Q fever pathogenesis.
- To analyze MMP gene expression and production in response to C. burnetii.
Main Methods:
- Microarray analysis and ELISA were used to study MMP gene expression and production in peripheral blood mononuclear cells (PBMCs).
- Single nucleotide polymorphisms (SNPs) in MMP genes were genotyped in patients and controls.
- Circulating MMP levels were compared between chronic Q fever patients and controls.
Main Results:
- C. burnetii up-regulated MMP pathway genes (MMP1, MMP7, MMP10, MMP19) in healthy PBMCs.
- C. burnetii induced MMP-1 and MMP-9 production in PBMCs from all groups.
- Specific MMP7 and MMP9 SNPs were more common in chronic Q fever patients, who also had higher circulating MMP-7 levels.
Conclusions:
- Coxiella burnetii-induced MMP production is a potential contributor to chronic Q fever development.
- MMPs may play a significant role in the pathogenesis of this persistent infection.
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