Skip to main content

Advertisement

SpringerLink
Log in

Increased Serum Levels of Matrix-metalloproteinase-9, Cyclo-oxygenase-2 and Prostaglandin E-2 in Patients with Chronic Obstructive Pulmonary Disease (COPD)

  • Original Research Article
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Chronic obstructive pulmonary disease (COPD), a heterogeneous lung disorder that is characterized by airflow obstruction and the third leading cause of death, globally. COPD is influenced by environmental and genetic factors. Here, we measured the serum level of matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and prostaglandin E-2 (PGE-2) and reveal the correlation between their levels in COPD subjects. In this study, we included a total of 79 COPD and 79 healthy controls. We assessed demographic profile, risk factors, respiratory symptoms, clinical history, COPD Assessment Test (CAT) score and spirometry. Further, we determined the serum levels of MMP-9, COX-2 and PGE-2 by enzyme-linked immunosorbent assay (ELISA). The correlation between their serum levels was also determined. Among the studied population age, gender, body mass index and socioeconomic status were comparable. Serum levels of MMP-9, COX-2 and PGE-2 were significantly increased in the COPD group than in healthy controls (P < 0.0001). Moreover, MMP-9, COX-2 and PGE-2 levels were increased with the GOLD grades and CAT score (> 10). Serum levels of MMP-9, COX-2 and PGE-2 was enhanced in patients with larger clinical history (> 20 years) than those with lower clinical history (< 10 years). Serum levels of MMP-9 and COX-2; MMP-9 and PGE-2; COX-2 and PGE-2 showed a positive correlation (P < 0.0001) with the COPD group. Our data demonstrate that serum levels of MMP-9, COX-2 and PGE-2 were correlated with the GOLD grade, CAT score and clinical history of the COPD group, pointing that they can be used as a indicators to understand the disease progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (2021 Report). 2020 Global Initiative for Chronic Obstructive Lung Disease, Inc. https://goldcopd.org/2021-gold-reports/ (assessed on 15 December 2020).

  2. Chen Y, Chen P, Hanaoka M, Droma Y, Kubo K. Enhanced levels of prostaglandin E2 and matrix metalloproteinase-2 correlate with the severity of airflow limitation in stable COPD. Respirology. 2008;13(7):1014–21.

    PubMed  Google Scholar 

  3. Uysal P, Uzun H. Relationship between circulating serpina3g, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 and-2 with chronic obstructive pulmonary disease severity. Biomolecules. 2019;9(2):62.

    Article  Google Scholar 

  4. Churg A, Zhou S, Wright JL. Matrix metalloproteinases in COPD. Eur Respir J. 2012;39:197–209.

    Article  CAS  Google Scholar 

  5. Greenlee KJ, Werb Z, Kheradmand F. Matrix metalloproteinases in lung: multiple, multifarious and multifaceted. Physiol Rev. 2007;87(1):69–98.

    Article  CAS  Google Scholar 

  6. Abd El-Fatah MF, Ghazy MA, Mostafa MS, El-Attar MM, Osman A. Identification of MMP-9 as a biomarker for detecting progression of chronic obstructive pulmonary disease. Biochem Cell Biol. 2015;93(6):541–7.

    Article  CAS  Google Scholar 

  7. Mitchell JA, Warner TD. Cyclo-oxygenase-2: pharmacology, physiology, biochemistry and relevance to NSAID therapy. Br J Pharmacol. 1999;128(6):1121–32.

    Article  CAS  Google Scholar 

  8. Shi Z, Chen Y, Pei Y, Long Y, Liu C, Cao J, et al. The role of cyclooxygenase-2 in the protection against apoptosis in vascular endothelial cells induced by cigarette smoking. J Thorac Dis. 2017;9(1):30–41.

    Article  Google Scholar 

  9. Lee K, Lee SH, Kim TH. The biology of prostaglandins and their role as a target for allergic airway disease therapy. Int J Mol Sci. 2020;21(5):1851.

    Article  CAS  Google Scholar 

  10. Zaslona Z, Peters-Golden M. Prostanoids in asthma and COPD: actions, dysregulation and therapeutic opportunities. Chest. 2015;148(5):1300–6.

    Article  Google Scholar 

  11. Lin CC, Lee IT, Yang YL, Lee CW, Kou YR, Yang CM. Induction of COX-2/PGE(2)/IL-6 is crucial for cigarette smoke extract-induced airway inflammation: role of TLR4-dependent NADPH oxidase activation. Free Radic Biol Med. 2010;48:240–54.

    Article  CAS  Google Scholar 

  12. Jiang S, Shan F, Zhang Y, Jiang L, Cheng Z. Increased serum IL-17 and decreased serum IL-10 and IL-35 levels correlate with the progression of COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:2483.

    Article  CAS  Google Scholar 

  13. Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D, et al. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India. 2009;57:163–70.

    CAS  PubMed  Google Scholar 

  14. Tan WC, Sin DD, Bourbeau J, Hernandez P, Chapman KR, Cowie R, et al. Characteristics of COPD in never-smokers and ever-smokers in the general population: results from the CanCOLD study. Thorax. 2015;70:822–9.

    Article  CAS  Google Scholar 

  15. Sharma R. Revised Kuppuswamy’s Socioeconomic Status Scale: explained and updated. Indian Pediatr. 2017;54:867–70.

    Article  Google Scholar 

  16. Beeh KM, Beier J, Kornmann O, Buhl R. Sputum matrix metalloproteinase-9, tissue inhibitor of metalloprotinease-1 and their molar ratio in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and healthy subjects. Respir Med. 2003;97(6):634–9.

    Article  CAS  Google Scholar 

  17. Linder R, Ronmark E, Pourazar J, Behndig A, Blomberg A, Lindberg A. Serum metalloproteinase-9 is related to COPD severity and symptoms-cross sectional data from a population based cohort-study. Respir Res. 2015;16(28):1–9.

    Google Scholar 

  18. Papakonstantinou E, Karakiulakis G, Batzios S, Savic S, et al. Acute exacerbations of COPD are associated with significant activation of matrix metalloproteinase 9 irrespectively of airway obstruction, emphysema and infection. Respir Res. 2015;16(1):78.

    Article  Google Scholar 

  19. Xu L, Bian W, Gu XH, Shen C. Genetic polymorphism in matrix metalloproteinase-9 and transforming growth factor-β1 and susceptibility to combined pulmonary fibrosis and emphysema in a Chinese population. Kaohsiung J Med Sci. 2017;33(3):124–9.

    Article  CAS  Google Scholar 

  20. Sng JJ, Prazakova S, Thomas PS, Herbert C. MMP-8, MMP-9 and Neutrophil Elastase in Peripheral Blood and Exhaled Breath Condensate in COPD. COPD. 2017;14(2):238–44.

    Article  Google Scholar 

  21. Cane JL, Mallia-Millanes B, Forrester DL, Knox AJ, Bolton CE, Johnson SR (2016) Matrix metalloproteinases-8 and-9 in the airways, blood and urine during exacerbations of COPD. COPD: Journal of Chronic Obstructive Pulmonary Disease. 13(1); 26–34.

  22. Xin XF, Zhao M, Li ZL, Song Y, Shi Y. Metalloproteinase-9/tissue inhibitor of metalloproteinase-1 in induced sputum in patients with asthma and chronic obstructive pulmonary disease and their relationship to airway inflammation and airflow limitation. Chinese J Tuberculosis Respir Dis. 2007;30(3):192–6.

    Google Scholar 

  23. Montuschi P, Kharitonov SA, Ciabattoni G, Barnes PJ. Exhaled leukotrienes and prostaglandins in COPD. Thorax. 2003;58:585–8.

    Article  CAS  Google Scholar 

  24. Bonanno A, Albano GD, Siena L, Montalbano AM, Riccobono L, Anzalone G, et al. Prostaglandin E2 possesses different potencies in inducing vascular endothelial growth factor and interleukin-8 production in COPD human lung fibroblasts. Prostaglandins Leukot Essent Fatty Acids. 2016;106:11–8.

    Article  CAS  Google Scholar 

  25. Taha R, Olivenstein R, Utsumi T, Ernst P, Barnes PJ, Rodger IW, et al. Prostaglandin H synthase 2 expression in airway cells from patients with asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161:636–40.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank to all the participants who had given their consent to participate in the study.

Funding

This work was supported by Council of Science and Technology, Uttar Pradesh (No: CST/SERPD/D-2477).

Author information

Author notes

  1. Ajay Kumar Verma and Anuj Kumar Pandey - Authors contributed equally

Authors and Affiliations

  1. Department of Respiratory Medicine, King George’s Medical University, Lucknow, 226003, Uttar Pradesh, India

    Ajay Kumar Verma, Anuj Kumar Pandey & Surya Kant

  2. Department of Pharmacology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, 226010, Uttar Pradesh, India

    Arpita Singh

  3. Department of Biochemistry, King George’s Medical University, Lucknow, 226003, Uttar Pradesh, India

    Abbas Ali Mahdi

  4. Department of Pulmonary & Critical Care Medicine, King George’s Medical University, Lucknow, 226003, Uttar Pradesh, India

    Ved Prakash

  5. Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India

    Kausar Mahmood Ansari

  6. Department of Pharmacology, King George’s Medical University, Lucknow, 226003, Uttar Pradesh, India

    Rakesh Kumar Dixit

  7. Department of Medicine, King George’s Medical University, Lucknow, 226003, Uttar Pradesh, India

    Shyam Chand Chaudhary

Authors
  1. Ajay Kumar Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anuj Kumar Pandey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arpita Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Surya Kant
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abbas Ali Mahdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ved Prakash
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kausar Mahmood Ansari
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rakesh Kumar Dixit
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shyam Chand Chaudhary
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: AKV, AKP; Data analysis:. AKV, AKP, AAM, VP; Funding: AKV; Investigation: AKP, AKV, AS, SK, AAM, VP, KMA, RKD, SCC; Experimental studies: AKV, AKP, AS, KMA; Validation: AKV, AKP, AS, SK, SCC, RKD; Manuscript writing & original draft: AKP, AKV, AS; Writing, review & editing: AKV, AKP, AS, SK, AAM, VP, KMA, RKD, SCC.

Corresponding author

Correspondence to Ajay Kumar Verma.

Ethics declarations

Conflict of interest

Authors declare no competing financial interest.

Consent for publication

Informed written consent was obtained from all the participants prior to enrolling in the study.

Ethical Approval

Study protocol was approved by Institutional Ethics Committee of the institution. And study was performed in accordance of approved protocol.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 128 kb)

Supplementary file2 (TIF 86 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Verma, A.K., Pandey, A.K., Singh, A. et al. Increased Serum Levels of Matrix-metalloproteinase-9, Cyclo-oxygenase-2 and Prostaglandin E-2 in Patients with Chronic Obstructive Pulmonary Disease (COPD). Ind J Clin Biochem 37, 169–177 (2022). https://doi.org/10.1007/s12291-021-00973-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12291-021-00973-2

Keywords

Search

Navigation