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

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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.

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Acknowledgements

This work was supported by the Ministry of Higher Education and by the Ministry of Public Health of the Tunisian Government. The authors wish to thank all the patients and controls who participated in this study.

Funding

The authors S. Bchir, S. Boumiza, H. ben Nasr, A. Garrouch, I. Kallel, Z. Tabka and K. Chahed declare that this study was funded by the Tunisian Ministry of Higher Education and Research (LR19ES09).

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Authors and Affiliations

  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, Soumaya Boumiza, Hela ben Nasr, Zouhair Tabka & Karim Chahed

  2. Institut Des Sciences Infirmières, Sousse, Tunisia

    Hela ben Nasr

  3. Service de Pneumo-Allergologie, CHU Farhat Hached, Sousse, Tunisia

    Abdelhamid Garrouch

  4. Laboratoire de Recherche Toxicologie Microbiologie Environnementale Et Santé LR17ES06, Faculté Des Sciences de Sfax, Université de Sfax, Sfax, Tunisia

    Imen Kallel

  5. Faculté Des Sciences de Sfax, Université de Sfax, Sfax, Tunisia

    Karim Chahed

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  1. Sarra Bchir
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  2. Soumaya Boumiza
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  3. Hela ben Nasr
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  4. Abdelhamid Garrouch
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  5. Imen Kallel
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  6. Zouhair Tabka
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  7. Karim Chahed
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Contributions

S. Bchir collected clinical samples, analyzed and interpreted data and drafted the manuscript. S. Boumiza and H. ben Nasr collected clinical samples and revised the manuscript. A. Garrouch and Z. Tabka recorded clinical characteristics of participants and revised the manuscript. I. Kallel provided critical technical support in data analysis. K. Chahed contributed to experimental design, analyzed and interpreted data and drafted the manuscript.

Corresponding author

Correspondence to Sarra Bchir.

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Conflict of interest

The authors S. Bchir, S. Boumiza, H. ben Nasr, A. Garrouch, I. Kallel, Z. Tabka and K. Chahed have no conflicts of interest that are directly relevant to the content of this article.

Ethical approval and informed consent

The study was approved by the local ethical committee of Farhat Hached Hospital (Sousse, Tunisia, approval number: 08–2011).

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Bchir, S., Boumiza, S., ben Nasr, H. et al. Impact of cathepsin D activity and C224T polymorphism (rs17571) on chronic obstructive pulmonary disease: correlations with oxidative and inflammatory markers. Clin Exp Med 21, 457–465 (2021). https://doi.org/10.1007/s10238-021-00692-1

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  • DOI: https://doi.org/10.1007/s10238-021-00692-1

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