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 mu M 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 mu M 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 mu M 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.