Sarra Bchir1, Soumaya Boumiza2, Hela Ben Nasr2,3, Abdelhamid Garrouch4, Imen Kallel5, Zouhair Tabka2, Karim Chahed2,6. 1. Laboratoire de Recherche LR19ES09, Physiologie de L'Exercice Et Physiopathologie : de L'Intégré Au Moléculaire Biologie, Médecine Et Santé, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia. sarra.bchir@yahoo.fr. 2. Laboratoire de Recherche LR19ES09, Physiologie de L'Exercice Et Physiopathologie : de L'Intégré Au Moléculaire Biologie, Médecine Et Santé, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia. 3. Institut Des Sciences Infirmières, Sousse, Tunisia. 4. Service de Pneumo-Allergologie, CHU Farhat Hached, Sousse, Tunisia. 5. Laboratoire de Recherche Toxicologie Microbiologie Environnementale Et Santé LR17ES06, Faculté Des Sciences de Sfax, Université de Sfax, Sfax, Tunisia. 6. Faculté Des Sciences de Sfax, Université de Sfax, Sfax, Tunisia.
Abstract
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-α), 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-α 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-α [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-α levels, particularly in COPD smokers.
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-α), 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-α 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-α [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-α levels, particularly in COPD smokers.