Acute cadmium exposure augments MMP-9 secretion and disturbs MMP-9/TIMP-1 balance

Background: Cadmium (Cd) is an extremely toxic metal commonly found in industrial work places, a food contaminant and a major component of cigarette smoke. Tobacco smoke and Cd inhalation result in alveolar inflammation, accumulation of immune cells and proteases/anti-proteases imbalance associated with chronic obstructive pulmonary disease and emphysema.

Objectives: We studied Cd toxicity on U-937 monocytoid cells and its influence on matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP1) levels.

Methods: U-937 cells were cultured and treated with either concentrations of 1.0, 10.0 or 50.0 μM cadmium chloride. Cytotoxicity percentages were measured by activity assay of lactate dehydrogenase released into culture medium of treated and the control cells. MMP-9 and TIMP-1 levels were determined by ELISA. Zymography technique was used to quantify MMP-9 gelatinolytic activity in culture media of U-937 cells. Alterations in MMP-9 and TIMP-1 gene expressions in response to Cd were analyzed by real-time PCR method.

Results: Cd found to be dose-dependently cytotoxic where 50.0 μM Cd significantly increased LDH leakage from the cells (p <0.05). MMP-9 levels measured by ELISA and zymography methods showed significant 44% and 48% increase, respectively, following exposure to 50.0 μM of Cd (p <0.05). Cd doses did not exert any effect on TIMP-1 levels. Alteration in MMP-9/TIMP-1 genes expressions in response to Cd found to be below a half fold increase for all doses which were not statistically significant.

Conclusion: These results suggest that Cd has direct detrimental effects on cell viability, MMPs activity and protease/anti-protease balance which may contribute to alveolar wall destruction and pulmonary diseases.