Cytokine profile in childhood asthma
DOI:
https://doi.org/10.20883/medical.e725Keywords:
asthma, cytokines, inflammatory proteins, biomarkersAbstract
Childhood asthma is a chronic airway disease, which pathogenesis is markedly heterogeneous–with multiple phenotypes defining visible characteristics and endotypes defining molecular mechanisms. Cytokines and chemokines released during inflammatory responses are key immune mediators. The cytokine response can largely determine the susceptibility to childhood asthma and its severity. The purpose of this study was to characterize the immune profile of childhood asthma. The study involved 26 children (3–18 years old), who were divided into 2 groups: study–with childhood asthma; control–without asthma. The innovative Bio-Plex method was used to determine the serum concentration of 37 inflammatory proteins in one experiment. The results were analyzed using univariate statistical tests. In the study group, the level of the 10 tested markers increased, while the level of the remaining 9 decreased compared to the control; a statistically significant reduction in concentration was obtained only for the MMP-1(p<0.05). According to the ROC curve, MMP-1 can be considered an effective discriminator of childhood asthma (p<0.05; AUC=0.752). Cytokines/chemokines may be useful in the diagnosis of childhood asthma and may also become a prognostic target in determining the phenotype/endotype of this condition. This study should be a prelude to and an incentive for more complex proteomic analyzes.
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References
Marko A, Ross KR. Severe Asthma in Childhood. Immunol Allergy Clin North Am. 2019, 39(2), 243-257. doi:10.1016/j.iac.2018.12.007.
Mallol J, Crane J, von Mutius E, et al. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis. Allergol Immunopathol (Madr). 2013, 41(2), 73-85. doi:10.1016/j.aller.2012.03.001.
Asher MI, García-Marcos L, Pearce NE, Strachan DP. Trends in worldwide asthma prevalence. Eur Respir J. 2020, 56(6), 2002094. doi:10.1183/13993003.02094-2020.
Moral L, Vizmanos G, Torres-Borrego J, et al. Asthma diagnosis in infants and preschool children: a systematic review of clinical guidelines. Allergol Immunopathol (Madr). 2019, 47(2), 107-121. doi:10.1016/j.aller.2018.05.002
Licari A, Castagnoli R, Brambilla I, et al. Asthma Endotyping and Biomarkers in Childhood Asthma. Pediatr Allergy Immunol Pulmonol. 2018, 31(2), 44-55. doi:10.1089/ped.2018.0886.
Matysiak, J.; Klupczynska, A.; Packi, K.; Mackowiak-Jakubowska, A.; Bręborowicz, A.; Pawlicka, O.; Olejniczak, K.; Kokot, Z.J.; Matysiak, J. Alterations in Serum-Free Amino Acid Profiles in Childhood Asthma. Int. J. Environ. Res. Public Health 2020, 17, 4758. https://doi.org/10.3390/ijerph17134758.
Boonpiyathad T, Sözener ZC, Satitsuksanoa P, Akdis CA. Immunologic mechanisms in asthma. Semin Immunol. 2019, 46, 101333. doi:10.1016/j.smim.2019.101333.
Packi, K.; Matysiak, J.; Klimczak, S.; Matuszewska, E.; Bręborowicz, A.; Pietkiewicz, D.; Matysiak, J. Analysis of the Serum Profile of Cytokines Involved in the T-Helper Cell Type 17 Immune Response Pathway in Atopic Children with Food Allergy. Int. J. Environ. Res. Public Health 2022, 19, 7877. https://doi.org/10.3390/ijerph19137877.
Robroeks CM, Rijkers GT, Jöbsis Q, et al. Increased cytokines, chemokines and soluble adhesion molecules in exhaled breath condensate of asthmatic children. Clin Exp Allergy. 2010, 40(1), 77-84. doi:10.1111/j.1365-2222.2009.03397.x.
Matsunaga K, Yanagisawa S, Ichikawa T, et al. Airway cytokine expression measured by means of protein array in exhaled breath condensate: correlation with physiologic properties in asthmatic patients. J Allergy Clin Immunol. 2006, 118(1), 84-90. doi:10.1016/j.jaci.2006.04.020.
Lin, S.-C.; Shi, L.-S.; Ye, Y.-L. Advanced Molecular Knowledge of Therapeutic Drugs and Natural Products Focusing on Inflammatory Cytokines in Asthma. Cells 2019, 8, 685. https://doi.org/10.3390/cells8070685.
Packi, K.; Matysiak, J.; Matuszewska, E.; Bręborowicz, A.; Kycler, Z.; Matysiak, J. New Biomarkers of Hymenoptera Venom Allergy in a Group of Inflammation Factors. Int. J. Environ. Res. Public Health 2021, 18, 4011. https://doi.org/10.3390/ijerph18084011.
Houser B. Bio-Rad's Bio-Plex® suspension array system, xMAP technology overview. Arch Physiol Biochem. 2012, 118(4), 192-196. doi:10.3109/13813455.2012.705301.
Chuang CK, Lin HY, Wang TJ, Huang SF, Lin SP. Bio-Plex immunoassay measuring the quantity of lysosomal N-acetylgalactosamine-6-sulfatase protein in dried blood spots for the screening of mucopolysaccharidosis IVA in newborn: a pilot study. BMJ Open. 2017, 7(7), e014410. Published 2017 Jul 13. doi:10.1136/bmjopen-2016-014410.
Xiao L, Wang Y, Kang R, et al. Development and application of a novel Bio-Plex suspension array system for high-throughput multiplexed nucleic acid detection of seven respiratory and reproductive pathogens in swine. J Virol Methods. 2018, 261, 104-111. doi:10.1016/j.jviromet.2018.08.017.
Kuhn N, Klinger B, Uhlitz F, et al. Mutation-specific effects of NRAS oncogenes in colorectal cancer cells. Adv Biol Regul. 2021, 79, 100778. doi:10.1016/j.jbior.2020.100778.
Kanda T, Yoshida A, Ogihara K, et al. Detection of cytokine storm in patients with achalasia using ELISA. Biomed Rep. 2021, 15(1), 62. doi:10.3892/br.2021.1438.
Ruan JW, Zhao JF, Li XL, et al. Characterizing the Neutrophilic Inflammation in Chronic Rhinosinusitis With Nasal Polyps. Front Cell Dev Biol. 2021, 9. 793073. doi:10.3389/fcell.2021.793073.
Martynova EV, Maksudova AN, Shakirova VG, et al. Urinary Clusterin Is Upregulated in Nephropathia Epidemica. Dis Markers. 2018, 2018, 8658507. doi:10.1155/2018/8658507.
Dahlen B, Shute J, Howarth P. Immunohistochemical localisation of the matrix metalloproteinases MMP-3 and MMP-9 within the airways in asthma. Thorax. 1999, 54(7), 590-596. doi:10.1136/thx.54.7.590
Arakaki PA, Marques MR, Santos MC. MMP-1 polymorphism and its relationship to pathological processes. J Biosci. 2009, 34(2), 313-320. doi:10.1007/s12038-009-0035-1.
Ingram J, Kraft M. Metalloproteinases as modulators of allergic asthma: therapeutic perspectives. Metalloproteinases In Medicine. 2015, 2, 61-74. https://doi.org/10.2147/MNM.S63614.
Liang L, Zhu DP, Guo SS, Zhang D, Zhang T. MMP-1 gene polymorphism in osteoporosis. Eur Rev Med Pharmacol Sci. 2019, 23, 67-72. doi:10.26355/eurrev_201908_18631.
Ertugrul AS, Dursun R, Dundar N, Avunduk MC, Hakki SS. MMP-1, MMP-9, and TIMP-1 levels in oral lichen planus patients with gingivitis or periodontitis. Arch Oral Biol. 2013, 58(7), 843-852. doi:10.1016/j.archoralbio.2013.01.015.
Rogers NK, Clements D, Dongre A, Harrison TW, Shaw D, Johnson SR. Extra-cellular matrix proteins induce matrix metalloproteinase-1 (MMP-1) activity and increase airway smooth muscle contraction in asthma. PLoS One. 2014, 9(2), e90565. doi:10.1371/journal.pone.0090565.
Naveed SU, Clements D, Jackson DJ, 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.
Morris CR, Poljakovic M, Lavrisha L, Machado L, Kuypers FA, Morris SM Jr. Decreased arginine bioavailability and increased serum arginase activity in asthma. Am J Respir Crit Care Med. 2004, 170(2), 148-153. doi:10.1164/rccm.200309-1304OC.
Sugai K, Kimura H, Miyaji Y, et al. MIP-1α level in nasopharyngeal aspirates at the first wheezing episode predicts recurrent wheezing. J Allergy Clin Immunol. 2016, 137(3), 774-781. doi:10.1016/j.jaci.2015.08.032.
Dahlen B, Shute J, Howarth P. Immunohistochemical localisation of the matrix metalloproteinases MMP-3 and MMP-9 within the airways in asthma. Thorax. 1999, 54(7), 590-596. doi:10.1136/thx.54.7.590.
earing, A., Beckett, P., Christodoulou, M. et al. Processing of tumour necrosis factor-α precursor by metalloproteinases. Nature. 1994, 370, 555–557 (1994). https://doi.org/10.1038/370555a0.
Ingram JL, Slade D, Church TD, Francisco D, Heck K, Sigmon RW, Ghio M, Murillo A, Firszt R, Lugogo NL, Que L, Sunday ME, Kraft M. Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13-Suppressed Elastin in Airway Fibroblasts in Asthma. Am J Respir Cell Mol Biol. 2016, 54(1), 41-50. doi: 10.1165/rcmb.2014-0290OC.
Lambrecht BN, Hammad H, Fahy JV. The Cytokines of Asthma. Immunity. 2019, 50(4), 975-991. doi:10.1016/j.immuni.2019.03.018.
Allahverdian S, Harada N, Singhera GK, Knight DA, Dorscheid DR. Secretion of IL-13 by airway epithelial cells enhances epithelial repair via HB-EGF. Am J Respir Cell Mol Biol. 2008, 38(2), 153-160. doi:10.1165/rcmb.2007-0173OC.
Cataldo DD, Gueders M, Munaut C, et al. Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases mRNA transcripts in the bronchial secretions of asthmatics. Lab Invest. 2004, 84(4), 418-424. doi:10.1038/labinvest.3700063.
Ohta Y, Hayashi M, Kanemaru T, Abe K, Ito Y, Oike M. Dual modulation of airway smooth muscle contraction by Th2 cytokines via matrix metalloproteinase-1 production. J Immunol. 2008, 180(6), 4191-4199. doi:10.4049/jimmunol.180.6.4191.
Kim HL, Woo SM, Choi WR, et al. Scopoletin downregulates MMP‑1 expression in human fibroblasts via inhibition of p38 phosphorylation. Int J Mol Med. 2018, 42(4), 2285-2293. doi:10.3892/ijmm.2018.3757.
Liu S-C, Tsai C-H, Wu T-Y, et al. Soya-cerebroside reduces IL-1β-induced MMP-1 production in chondrocytes and inhibits cartilage deg-radation: implications for the treatment of osteoarthritis. Food and Agricultural Immunology. 2019, 30, 620-632. doi: 10.1080/09540105.2019.1611745.
Kang KA, Zhang R, Piao MJ, et al. Inhibitory effects of triphlorethol-A on MMP-1 induced by oxidative stress in human keratinocytes via ERK and AP-1 inhibition. J Toxicol Environ Health A. 2008, 71(15), 992-999. doi:10.1080/01932690801934653.
Broniarczyk-Dyła G, Prusińska-Bartoś M, Grzegorczyk J, Jarzębska M, Wawrzycka-Kaflik A. Soluble receptors CD30 and CD26 in serum of patients with atopic dermatitis as markers of disease activity. Adv Dermatol Allergol, 2005, 22(5), 219–226, 2005.
Fölster-Holst R, Henseler T, Wehde J, et al. Soluble CD30 plasma concentrations correlate with disease activity in patients with atopic dermatitis. Acta Derm Venereol. 2002, 82(4), 245-248. doi:10.1080/000155502320323180.
Polte T, Behrendt AK, Hansen G. Direct evidence for a critical role of CD30 in the development of allergic asthma. J Allergy Clin Immunol. 2006, 118(4), 942-948. doi:10.1016/j.jaci.2006.07.014.
Boonpiyathad S, Pornsuriyasak P, Buranapraditkun S, Klaewsongkram J. Interleukin-2 levels in exhaled breath condensates, asthma severity, and asthma control in nonallergic asthma . Allergy Asthma Proc. 2013, 34(5), e35-e41. doi:10.2500/aap.2013.34.3680.
Raundhal M, Morse C, Khare A, et al. High IFN-γ and low SLPI mark severe asthma in mice and humans. J Clin Invest. 2015, 125(8), 3037-3050. doi:10.1172/JCI80911.
Charrad R, Kaabachi W, Rafrafi A, Berraies A, Hamzaoui K, Hamzaoui A. IL-8 Gene Variants and Expression in Childhood Asthma. Lung. 2017;195(6):749-757. doi:10.1007/s00408-017-0058-6.
Kim SY, Kim JD, Sol IS, et al. Sputum TWEAK expression correlates with severity and degree of control in non-eosinophilic childhood asthma. Pediatr Allergy Immunol. 2018, 29(1), 42-49. doi:10.1111/pai.12827.
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