MiR-185-5p measurement assists in reflecting Th1/Th2 cell imbalance, inflammatory cytokine production, and exacerbation risk for childhood asthma
Main Article Content
Childhood asthma, exacerbation severity, miR-185-5p, inflammatory cytokines, Th1/Th2 cells
Background: MicroRNA (miR)-185-5p participates in the pathology of asthma by regulating immune imbalance, inflammation, periostin synthesis, and smooth muscle contraction. This study intended to explore the dysregulation of miR-185p and its correlation with T-helper (Th)1, Th2 cells, and inflammatory cytokines in childhood asthma.
Methods: In 150 childhood asthma patients and 30 healthy controls (HCs), miR-185-5p from peripheral blood mononuclear cells was detected using reverse transcription-quantitative polymerase chain reaction, Th cells from peripheral blood samples were detected using flow cytometry, inflammatory cytokines from serum samples were detected using enzyme-linked immunosorbent assay.
Results: MiR-185-5p was increased in childhood asthma patients versus HCs [median (interquartile range (IQR)): 2.315 (1.770–3.855) versus 1.005 (0.655–1.520)] (P < 0.001). Meanwhile, miR-185-5p was negatively associated with Th1 cells (P = 0.035) but positively correlated with Th2 cells (P = 0.006) and IL-4 (P = 0.003) in childhood asthma patients; however, miR-185-5p was not linked to Th1 cells, Th2 cells, IFN-γ, or IL-4 in HCs (all P > 0.05). In addition, miR-185-5p was positively related to TNF-α (P < 0.001), IL-1β (P = 0.015), and IL-6 (P = 0.008) in childhood asthma patients, miR-185-5p was only linked to TNF-α (P = 0.040) but not IL-1β or IL-6 (both P > 0.05) in HCs. Moreover, miR-185-5p was increased in exacerbated childhood asthma patients versus remissive patients [median (IQR): 3.170 (2.070–4.905) versus 1.900 (1.525–2.615)] (P < 0.001). Besides, miR-185-5p was highest in patients with severe exacerbation followed by patients with moderate exacerbation, and lowest in patients with mild exacerbation (P = 0.010).
Conclusion: MiR-185-5p is associated with imbalanced Th1/Th2 cells, increased inflammatory cytokines along with elevated exacerbation risk, and severity in childhood asthma patients.
2. Miller RL, Grayson MH, Strothman K. Advances in asthma: New understandings of asthma's natural history, risk factors, underlying mechanisms, and clinical management. J Allergy Clin Immunol. 2021;148(6):1430–41. 10.1016/j.jaci.2021.10.001
3. Arakawa H, Adachi Y, Ebisawa M, Fujisawa T, Committee for Japanese Pediatric Guideline for Childhood A, Japanese Society of Pediatric A, et al. Japanese guidelines for childhood asthma 2020. Allergol Int. 2020;69(3):314–30. 10.1016/j.alit.2020.02.005
4. Alwarith J, Kahleova H, Crosby L, Brooks A, Brandon L, Levin SM, et al. The role of nutrition in asthma prevention and treatment. Nutr Rev. 2020;78(11):928–38. 10.1093/nutrit/nuaa005
5. Martin J, Townshend J, Brodlie M. Diagnosis and management of asthma in children. BMJ Paediatr Open. 2022;6(1). 10.1136/bmjpo-2021-001277
6. Wahidi MM, Kraft M. Bronchial thermoplasty for severe asthma. Am J Respir Crit Care Med. 2012;185(7):709–14. 10.1164/rccm.201105-0883CI
7. Fuchs O, Bahmer T, Rabe KF, von Mutius E. Asthma transition from childhood into adulthood. Lancet Respir Med. 2017;5(3):224–34. 10.1016/S2213-2600(16)30187-4
8. Stefansdottir AR, Ludviksson BR, Ardal B, Haraldsson A. Longitudinal asthma and allergy study showed that childhood symptoms frequently persisted into adulthood. Acta Paediatr. 2022;111(2):418–23. 10.1111/apa.16118
9. To M, Tsuzuki R, Katsube O, Yamawaki S, Soeda S, Kono Y, et al. Persistent Asthma from Childhood to Adulthood Presents a Distinct Phenotype of Adult Asthma. J Allergy Clin Immunol Pract. 2020;8(6):1921–7 e2. 10.1016/j.jaip.2020.01.011
10. Pijnenburg MW, Fleming L. Advances in understanding and reducing the burden of severe asthma in children. Lancet Respir Med. 2020;8(10):1032–44. 10.1016/S2213-2600(20)30399-4
11. McGeachie MJ, Yates KP, Zhou X, Guo F, Sternberg AL, Van Natta ML, et al. Patterns of growth and decline in lung function in persistent childhood asthma. N Engl J Med. 2016;374(19):1842–52. 10.1056/NEJMoa1513737
12. Castagnoli R, Marseglia A, Brambilla I, Marseglia GL, Licari A. Severe uncontrolled asthma in children: practical approach on diagnosis and management. Minerva Pediatr. 2020;72(3):196–205. 10.23736/S0026-4946.20.05818-1
13. Plaza-Gonzalez S, Zabala-Banos MDC, Astasio-Picado A, Jurado-Palomo J. Psychological and sociocultural determinants in childhood asthma disease: impact on quality of life. Int J Environ Res Public Health. 2022;19(5):2652. 10.3390/ijerph19052652
14. Ma X, Liu H, Zhu J, Zhang C, Peng Y, Mao Z, et al. miR-185-5p regulates inflammation and phagocytosis through CDC42/JNK pathway in macrophages. Genes. 2022;13(3):468. 10.3390/genes13030468
15. Sun Y, Wang MJ, Cao XT, Liu WY, Chen HY, Ding XQ, et al. Expression of MicroRNAs in peripheral blood of patients with primary immune thrombocytopenia and its correlation with the imbalance of Th1/Th2 Cell. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021;29(5):1570–6. 10.19746/j.cnki.issn.1009-2137.2021.05.031
16. Yang YL, Pan YQ, He BS, Zhong TY. Regulatory T cells and Th1/Th2 in peripheral blood and their roles in asthmatic children. Transl Pediatr. 2013;2(1):27–33. 10.3978/j.issn.2224-4336.2012.04.03
17. Zhu C, Zhang L, Liu Z, Li C, Bai Y, Wang L. Atractylenolide III reduces NLRP3 inflammasome activation and Th1/Th2 imbalances in both in vitro and in vivo models of asthma. Clin Exp Pharmacol Physiol. 2020;47(8):1360–7. 10.1111/1440-1681.13306
18. Peebles RS, Jr., Aronica MA. Proinflammatory Pathways in the Pathogenesis of Asthma. Clin Chest Med. 2019;40(1):29–50. 10.1016/j.ccm.2018.10.014
19. Rodrigo-Munoz JM, Canas JA, Sastre B, Gil-Martinez M, Garcia Latorre R, Sastre J, et al. Role of miR-185-5p as modulator of periostin synthesis and smooth muscle contraction in asthma. J Cell Physiol. 2022;237(2):1498–508. 10.1002/jcp.30620
20. Asthma GIf. Global strategy for asthma management and prevention. GINA Report. 2022.
21. Papadopoulos NG, Arakawa H, Carlsen KH, Custovic A, Gern J, Lemanske R, et al. International consensus on (ICON) pediatric asthma. Allergy. 2012;67(8):976–97. 10.1111/j.1398-9995.2012.02865.x
22. Hao Y, Li Y, Li H, Lyu M, Zhang D, Fu R, et al. Increased plasma sCXCL16 levels may have a relationship with Th1/Th2 imbalance in primary immune thrombocytopenia. Cytokine. 2017;99:124–31. 10.1016/j.cyto.2017.08.024
23. Mousavi SR, Tahmasebivand M, Khorrami M, Ayromlou H, Khalili SK, Khorvash F, et al. Connection of miR-185 and miR-320a expression levels with response to interferon-beta in multiple sclerosis patients. Mult Scler Relat Disord. 2020;44:102264. 10.1016/j.msard.2020.102264
24. Kaushik AC, Wu Q, Lin L, Li H, Zhao L, Wen Z, et al. Exosomal ncRNAs profiling of mycobacterial infection identified miRNA-185-5p as a novel biomarker for tuberculosis. Brief Bioinform. 2021;22(6):bbab210. 10.1093/bib/bbab210
25. Xu L, Yi M, Tan Y, Yi Z, Zhang Y. A comprehensive analysis of microRNAs as diagnostic biomarkers for asthma. Ther Adv Respir Dis. 2020;14:1753466620981863. 10.1177/1753466620981863
26. Rodrigo-Munoz JM, Canas JA, Sastre B, Rego N, Greif G, Rial M, et al. Asthma diagnosis using integrated analysis of eosinophil microRNAs. Allergy. 2019;74(3):507–17. 10.1111/all.13570
27. Zhao YB, Li W, Zhang Q, Yin Y, Yang CJ, Xu WX, et al. Distinct miRNA Gene Expression Profiles Among the Nodule Tissues of Lung Sarcoidosis, Tuberculous Lymphadenitis and Normal Healthy Control Individuals. Front Med (Lausanne). 2020;7:527433. 10.3389/fmed.2020.527433
28. Yadava SM, Feng A, Parobchak N, Wang B, Rosen T. miR-15b-5p promotes expression of proinflammatory cytokines in human placenta by inhibiting Apelin signaling pathway. Placenta. 2021;104:8–15. 10.1016/j.placenta.2020.11.002
29. Li G, Qin Y, Qin S, Zhou X, Zhao W, Zhang D. Circ_WBSCR17 aggravates inflammatory responses and fibrosis by targeting miR-185-5p/SOX6 regulatory axis in high glucose--induced human kidney tubular cells. Life Sci. 2020;259:118269. 10.1016/j.lfs.2020.118269
30. Carnino JM, Lee H, He X, Groot M, Jin Y. Extracellular vesicle--cargo miR-185-5p reflects type II alveolar cell death after oxidative stress. Cell Death Discov. 2020;6:82. 10.1038/s41420-020-00317-8