Impact of cathepsin D activity and C224T polymorphism (rs17571) on chronic obstructive pulmonary disease: correlations with oxidative and inflammatory markers

Background Cathepsin D (CTSD) is an aspartyl proteinase that plays an important role in protein degradation, antigen processing and apoptosis. It has been associated with several pathologies such as cancer, Alzheimer's disease and inflammatory disorders. Its function in lung diseases remains, however, controversial. In the current study, we determined CTSD activity in serum of patients with chronic obstructive pulmonary disease (COPD) and evaluated the correlations between this proteinase and inflammatory and oxidative parameters. We also investigated the impact of a CTSD C224T polymorphism on enzyme activity and clinicopathological parameters. Methods Our population included 211 healthy controls and 138 patients with COPD. CTSD activity, MMPs (-1/-7/-12), cytokines (IL-6, TNF-alpha), malondialdehyde (MDA), nitric oxide and peroxynitrite levels were measured in patients and controls using standard methods. Genotyping of CTSD C224T polymorphism was determined using PCR-RFLP. Results Our results showed an increased CTSD activity in COPD patients compared to healthy controls (4.87 [3.99-6.07] vs. 3.94 [2.91-5.84], respectively, p < 0.001). COPD smokers presented also a higher CTSD activity when compared to nonsmokers (4.91[3.98-6.18] vs. 4.65[4.16-5.82], respectively, p = 0.01), while no differences were found when subjects were compared according to their GOLD stages. The activity of this proteinase was not dependent on the C224T polymorphism because we did not found any influence of this SNP on proteinase activity among patients and controls. Furthermore, our data provide the first evidence of the interrelationships between CTSD activity and both MMPs and TNF-alpha levels (MMP-1[r = - 0.4; p = 0.02], MMP-7[r = 0.37; p = 0.04], MMP-12[r = 0.43; p = 0.02], TNF-alpha [r = 0.89, p = 0.001]) in COPD smokers. There were no correlations, however, between CTSD activity and oxidative stress parameters in controls and patients. Conclusion Our findings suggest that CTSD could be a relevant marker for COPD disease. Alteration of CTSD activity may be related to increased MMPs and TNF-alpha levels, particularly in COPD smokers.

Automated summary

The study found that patients with chronic obstructive pulmonary disease (COPD) had higher Cathepsin D (CTSD) activity compared to healthy controls, especially in smokers. The increased CTSD activity may be related to elevated levels of MMPs and TNF-alpha, particularly in COPD smokers, but not correlated with oxidative stress parameters.