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Published on: May 21, 2021
Metalloproteinase function in chronic rhinosinusitis with nasal polyposis
Katriina Kostamo1, Taina Tervahartiala, Timo Sorsa
1Department of Otorhinolaryngology, Helsinki University Central Hospital, Institute of Dentistry, University of Helsinki, Helsinki, Finland. b.k.kostamo@amc.uva.nl
Objectives:
Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma share characteristic inflammatory features and histopathologic findings of airway remodeling. Remodeling, which is controlled by matrix metalloproteinases (MMP), is a key event in the pathogenesis of asthma. The MMP functions have rarely been evaluated in CRSwNP.
Study Design:
Prospective and in vivo.
Methods:
MMP-7, MMP-8, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 concentrations were analyzed by enzyme-linked immunosorbent assay and their molecular forms by Western immunoblotting and gelatin zymography in 24 patients operated on for CRSwNP and in nasal lavages from 19 healthy controls. MMP function, protective or destructive, was evaluated by comparing MMP/TIMP-1 levels with the disease activity, estimated by tissue eosinophilia and a need for re-operations.
Results:
Significantly increased levels of MMP-8/TIMP-1 and MMP-9/TIMP-1 were found in patients without tissue eosinophilia relative to eosinophil-positive CRSwNP patients and controls, as well as in patients who did not require re-operation in comparison with re-operated patients. In eosinophil-positive and re-operated patients, these parameters were within the same range than in controls.
Conclusions:
Proteolytic spectrum is different in eosinophilic and noneosinophilic CRSwNP, suggesting a new mechanism for eosinophil accumulation in the disease pathogenesis. Enhanced MMP-8 and MMP-9 expression was associated with a better prognosis/clinical outcome, and thus these results may represent a synergic, protective role of MMP-8 and MMP-9 in host response in CRSwNP. Because synthetic MMP inhibitors, capable of equilibrating the unfavorable MMP/TIMP-ratio, may be of potential therapeutic value in chronic respiratory tract diseases, the MMP functions in inflammatory conditions need to be carefully established.
Insights
Matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinase (TIMP)-1 levels differ in chronic rhinosinusitis with nasal polyposis (CRSwNP). Enhanced MMP-8 and MMP-9 expression correlated with better outcomes, suggesting a protective role in CRSwNP.
Area of Science:
- Immunology
- Respiratory Medicine
- Biochemistry
Background:
- Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma share inflammatory pathways and airway remodeling.
- Matrix metalloproteinases (MMPs) are key regulators of airway remodeling, but their role in CRSwNP is not well understood.
Purpose of the Study:
- To evaluate the function of MMPs in CRSwNP.
- To investigate the relationship between MMP levels, tissue eosinophilia, and the need for re-operation in CRSwNP patients.
Main Methods:
- Prospective in vivo study analyzing MMP-7, MMP-8, MMP-9, and TIMP-1 concentrations in 24 CRSwNP patients and 19 healthy controls.
- Enzyme-linked immunosorbent assay, Western immunoblotting, and gelatin zymography were used to measure MMP levels and molecular forms.
- MMP/TIMP-1 ratios were compared with disease activity (tissue eosinophilia, re-operation history).
Main Results:
- Significantly higher MMP-8/TIMP-1 and MMP-9/TIMP-1 levels were observed in patients without tissue eosinophilia and those not requiring re-operation.
- In contrast, eosinophil-positive and re-operated patients showed MMP/TIMP-1 levels similar to controls.
- These findings indicate distinct proteolytic profiles in different CRSwNP phenotypes.
Conclusions:
- The proteolytic spectrum in CRSwNP varies between eosinophilic and non-eosinophilic subtypes, suggesting novel mechanisms for eosinophil recruitment.
- Elevated MMP-8 and MMP-9 expression is associated with improved clinical outcomes, pointing to a potential protective role in CRSwNP.
- Understanding MMP functions is crucial for developing targeted therapies for chronic respiratory diseases.
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