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Correlation between MMP-9 and MMP-9/ TIMPs Complex with Pulmonary Function in Sulfur Mustard Exposed Civilians:
Sara Ghaffarpour1, Tooba Ghazanfari1, Sussan Kabudanian Ardestani2
11)Immunoregulation Research Center, Shahed University, Tehran, I.R. Iran.2)Department of Immunology, Shahed University, Tehran, I.R. Iran.
Background:
Matrix metalloproteinases (MMPs) are a family of proteinases and have the vigorous capacity to degrade all parts of the extracellular matrix. MMP enzymes strongly participate in physiological processes such as normal tissue remodeling and wound healing and in pathology of pulmonary diseases. They are released in response to environmental stimuli such as toxins and regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Sulfur mustard (SM) is a chemical toxic which can cause severe permanent damages to lung tissues. The aim of this study was assessing the possible role of MMP-9 and TIMPs in SM-induced lung symptoms and signs in exposed patients 20 years after exposure.
Methods:
Totally, 372 male volunteers with a history of SM- exposure and 128 age- and sex-matched unexposed controls participated and were divided into three groups: normal, mild and moderate-severe. All participants underwent clinical evaluation and pulmonary function tests and serum concentrations of MMP-9 and its inhibitors were measured using the ELISA technique.
Results:
Serum level of MMP-9 was increased in the SM exposed group who had moderate-severe pulmonary complications compared with the SM exposed with normal lung (2.321 ± 2.836 vs. 1.546 ± 2.176, P = 0.001) while only the MMP-9/TIMP-4 complex was elevated in the SM exposed with normal lung individuals compared to its corresponding control group (85 ± 265 vs. 82 ± 222, P = 0.025). Although MMP-9 and its inhibitors did not show any correlation with spirometry findings, elevated circulating MMP-9 was detected in SM exposed patients with chronic chough and hemoptysis (P = 0.013 and P = 0.013 respectively).
Conclusion:
High level of tissue disruption and remodeling mediators could influence lung structure in long-term after SM-exposure. The correlation of clinical evaluation with these factors efficiently helps us to identify important effectors.
Insights
Long-term sulfur mustard (SM) exposure can increase matrix metalloproteinase-9 (MMP-9) levels, potentially influencing lung structure and symptoms like chronic cough and hemoptysis in survivors.
Area of Science:
- Pulmonary Medicine
- Toxicology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) degrade extracellular matrix and are involved in tissue remodeling and pulmonary diseases.
- Tissue inhibitors of metalloproteinases (TIMPs) regulate MMP activity.
- Sulfur mustard (SM) exposure causes severe lung damage.
Purpose of the Study:
- To assess the role of MMP-9 and TIMPs in long-term lung symptoms after SM exposure.
- To investigate the relationship between MMP-9, TIMPs, and pulmonary function in SM survivors.
Main Methods:
- 372 male SM-exposed volunteers and 128 controls were evaluated.
- Participants were categorized into normal, mild, and moderate-severe lung complication groups.
- Serum MMP-9 and TIMP levels were measured using ELISA, alongside clinical and pulmonary function tests.
Main Results:
- Elevated serum MMP-9 was observed in SM-exposed individuals with moderate-severe lung complications.
- The MMP-9/TIMP-4 complex was higher in SM-exposed individuals with normal lung function compared to controls.
- Elevated MMP-9 correlated with chronic cough and hemoptysis in SM-exposed patients, independent of spirometry findings.
Conclusions:
- Mediators of tissue disruption and remodeling, like MMP-9, may impact lung structure long after SM exposure.
- Clinical evaluation combined with MMP-9 and TIMP assessment can identify key factors in long-term SM-induced lung damage.
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