Matrix metalloproteinase-9 and monocyte chemotactic protein-1 in patients with bronchial asthma combined with type 2 diabetes mellitus

Objective: to study the content of MMP-9 and MCP-1 in patients with exacerbation of bronchial asthma combined with type 2 diabetes mellitus and exacerbation of bronchial asthma without of comorbid DM.

Materials and methods: 70 patients with moderate exacerbations of bronchial asthma (BA), including 36 patients with BA combined with type 2 diabetes mellitus (T2DM) (group I) and 34 patients with BA exacerbations without DM (group II), aged 38.8±2.7 years were observed. All patients had their serum and exhaled air condensate (EAC) concentrations of matrix metalloproteinase-9 (MMP-9) and monocyte chemotactic protein (MCP)-1 measured by enzyme-linked immunosorbent assay, as well as their monocyte phagocytic activity measured by the spontaneous test with nitroblue tetrazolium (NBT- test), phagocytic index (PI), and phagocytic number (PN).

Results: in patients of Group I, the concentrations of MMP-9 and MCP-1 in the blood serum exceeded those in Group II and the control group, as well as those in the ACE. The detected correlations between the studied indicators, between each indicator and the FEV₁ and HbA₁C levels, indicated their close relationship with each other in the exacerbation of BA combined with T2DM, and the negative impact of type 2 DM on the indicators. The results of the NBT-test in patients of groups I and II did not differ significantly, but were 1.5 times (p<0,05) higher than the control values and positively correlated with the value of MCP-1 in both groups of patients with BA. The phagocytic capacity of monocytes, despite the increased synthetic activity in patients of group I, was reduced. Thus, the РI in patients of Group I was 1.7 times (p<0,001) lower than in the control group, and similar in patients of Group II. The number of phagocytic cells in patients of Group I was 1.6 times (p<0.05) lower than in Group II, but significantly higher than in the control group.

Conclusions: patients with exacerbation of BA and BA combined with T2DM have a high concentration of MMP-9 and MCP-1 in the blood serum and EAC. The MMP-9 indicator in patients with BA combined with T2DM was noted to be the highest in EAC compared to the blood serum in these patients and compared to the concentration in the blood serum by 1.2 times (p<0.05). In patients with the association of BA and T2DM, a functional imbalance of phagocytic cells was revealed with a decrease in the number of cells capable of phagocytosis, along with an increase in the number of absorbed particles in phagocytic monocytes and increased production of MCP-1. The identified correlations between the values of the studied factors, bronchial patency, and HbA1c in patients with BA combined with T2DM may confirm their involvement in destructive and fibrotic processes in the TB.

1. Ivanov V., Rubeko E., Sorokina L., Mineev V., Bystrova A., Trofimov V. Bronchial asthma concurrent with type 2 diabetes mellitus: clinical and pathogenetic features. Vrach. 2016;7:36-38. (In Russ.) eLIBRARY ID: 26486722 EDN: WHPVKT

2. Rogova L.N., Shesternina N.V., Zamechnik T.V., Fastova I.A. Matrix metalloproteinases, their role in physiological and pathological processes (review) Bulletin of New Medical Technologies. 2011;18(2):86–90. (In Russ.) eLIBRARY ID: 16767924 EDN: OCYGFN

3. Kolotov K.A., Rasputin P.G. Monocytic chemotactic protein-1 in physiology and medicine (review of literature). Perm Medical Journal. 2018;35(3):99-105. (In Russ.) DOI: 10.17816/pmj35399-105

4. Naveed SU, Clements D, Jackson DJ, Philp C, Billington CK, Soomro I, et al. Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity. Am J Respir Crit Care Med. 2017;195(8):1000-1009. DOI: 10.1164/rccm.201604-0822OC

5. Kajlina A.N., Ogorodova L.M., Chasovskikh Yu.P., Kremer E.E. Indices of matrix metalloproteinases (MMP-2, MMP-9, TIMP-1) with juvenile arthritis in children. Bulletin of the Russian Academy of Medical Sciences. 2013;68(7):36-41. (In Russ.) eLIBRARY ID: 19671732 EDN: QOMJYT

6. Potapova N.L., Gaimolenko I.N. Biomarkers of Respiratory Tract Remodelling in Bronchial Asthma. Doctor.Ru. 2020;19(11):27–31. (in Russ.). DOI: 10.31550/1727-2378-2020-19-11-27-31

7. Gladkikh N.N., Yagoda A.V., Dzhazaeva M.B. Some indicators of the matrix metalloproteinase system in connective tissue dysplasia. Therapy. 2018;6(24):72-77. (In Russ.) https://doi.org/10.18565/therapy.2018.6.72-77.

8. Davydova I.V., Yatsyk G.V., Bershova T.V., Basargina M.A., Bakanov M.I. Matrix metalloproteinases as biomarkers of bronchopulmonary dysplasia formation in children. Pulmonologiya. 2009;(4):80-84. (In Russ.) DOI: 10.18093/0869-0189-2009-4-80-84

9. Adamyan LV, Manukyan LM, Loginova ON, Arslanyan KN, Zayratyants VO. The role of matrix metalloproteinases in the pathogenesis of endometriosis (literature review). Russian Journal of Human Reproduction. 2020;26(2):95‑103. (In Russ.) DOI: 10.17116/repro20202602195

10. Chung FT, Huang HY, Lo CY, Huang YC, Lin CW, He CC, et al. Increased Ratio of Matrix Metalloproteinase-9 (MMP-9)/Tissue Inhibitor Metalloproteinase-1 from Alveolar Macrophages in Chronic Asthma with a Fast Decline in FEV1 at 5-Year Follow-up. J Clin Med. 2019;8(9):1451. DOI: 10.3390/jcm8091451

11. Lebedenko A.A., Semernik O.E., Dudareva M.V., Tyurina E.B. The role of matrix metalloproteinase-9 in the genesis of chronic bronchi inflammation in children with bronchial asthma. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2020;65(2):49-54. (In Russ.) DOI: 10.21508/1027-4065-2020-65-2-49-54

12. Granata F, Frattini A, Loffredo S, Del Prete A, Sozzani S, Marone G, et al. Signaling events involved in cytokine and chemokine production induced by secretory phospholipase A2 in human lung macrophages. Eur J Immunol. 2006;36(7):1938-1950. DOI: 10.1002/eji.200535567

13. Skiba T.A. Metabolic stress and stress-limiting mechanisms in bronchial asthma combined with type 2 diabetes mellitus. South Russian Journal of Therapeutic Practice. 2024;5(1):47-52. (In Russ.) DOI: 10.21886/2712-8156-2024-5-1-47-52

14. Aznabaeva L.F., Gantseva Kh.Kh., Aflyatunova S.F. Monocyte chemotactic protein in immunopathogenesis of chronic obstructive pulmonary disease . Creative Surgery and Oncology. 2011;(1):85-89. (In Russ.) eLIBRARY ID: 17300532 EDN: OOPHAT