Journal of Isfahan Medical School

Journal of Isfahan Medical School

The Relationship between the Genetic Polymorphisms of Interleukin-33 (IL-33) and Interleukin-1 Receptor-Like 1 (IL1R1) with the Levels of Interleukin-33 in Patients with Asthma and Multiple Sclerosis

Document Type : Original Article (s)

Authors
Maryam Ahmadi 1
Nahid Eskandari 2
Fereshteh Ale-Sahebfosoul 2
Mansour Salehi 3
Ramin Ghasemi 4
1 MSc Student, Department of Immunology, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
2 Assistant Professor, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Associate Professor, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
4 Asthma and Allergy Specialist, Isfahan Asthma and Allergy Clinic, Isfahan, Iran
Abstract
Background: Recent evidence suggests that the interleukin-33/interleukin-1 receptor-like 1 (IL-33/IL1RL1) axis plays a critical role in autoimmune and inflammatory disorders; however, its mechanistic role in these diseases has not been clearly defined. The present study aimed to investigate the frequency of rs1342326 polymorphism of IL-33 gene and rs10204137 polymorphism of IL1RL1 gene with serum levels of IL-33 in multiple sclerosis (MS), asthma and healthy subjects In Isfahan Province, Iran.Methods: Samples were taken from the patients with asthma (140) or multiple sclerosis (140) and healthy controls (72). Different genotypes of T/G or G/A polymorphisms were studied using the high-resolution melting real-time polymerase chain reaction (HRM real-time PCR) technique. Serum levels of IL-33 were measured via enzyme-linked immunosorbent assay (ELISA). Findings: There was not any relationship between the frequency of polymorphism rs10204137 of IL1RL1 gene and susceptibility to multiple sclerosis or asthma. There was no significant correlation between the frequency of rs1342326 polymorphism of IL-33 gene in healthy subjects compared to those with asthma or multiple sclerosis. Serum levels of IL-33 were higher than in patients with multiple sclerosis or asthma compared to healthy subjects.Conclusion: Serum levels of IL-33 in the two groups of patient increased substantially compared to the controls.
Keywords
Interleukin-33 (IL-33)
Multiple Sclerosis
Asthma
Polymorphism
  1. Bousquet J, Clark TJ, Hurd S, Khaltaev N, Lenfant C, O'byrne P, et al. GINA guidelines on asthma and beyond. Allergy 2007; 62(2): 102-12.
  2. Heidarnia MA, Entezari A, Moein M, Mehrabi Y, Pourpak Z. Prevalence of asthma symptom in Iran: a meta-analysis. Pajouhesh Dar Pezeshki 2007; 31(3): 217-25. [In Persian].
  3. Larche M, Robinson DS, Kay AB. The role of T lymphocytes in the pathogenesis of asthma. J Allergy Clin Immunol 2003; 111(3): 450-63.
  4. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005; 23(5): 479-90.
  5. Allakhverdi Z, Smith DE, Comeau MR, Delespesse G. Cutting edge: The ST2 ligand IL-33 potently activates and drives maturation of human mast cells. J Immunol 2007; 179(4): 2051-4.
  6. Xu D, Chan WL, Leung BP, Huang F, Wheeler R, Piedrafita D, et al. Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells. J Exp Med 1998; 187(5): 787-94.
  7. Kondo Y, Yoshimoto T, Yasuda K, Futatsugi-Yumikura S, Morimoto M, Hayashi N, et al. Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system. Int Immunol 2008; 20(6): 791-800.
  8. Oshikawa K, Kuroiwa K, Tago K, Iwahana H, Yanagisawa K, Ohno S, et al. Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation. Am J Respir Crit Care Med 2001; 164(2): 277-81.
  9. Prefontaine D, Lajoie-Kadoch S, Foley S, Audusseau S, Olivenstein R, Halayko AJ, et al. Increased expression of IL-33 in severe asthma: evidence of expression by airway smooth muscle cells. J Immunol 2009; 183(8): 5094-103.
  10. Prefontaine D, Nadigel J, Chouiali F, Audusseau S, Semlali A, Chakir J, et al. Increased IL-33 expression by epithelial cells in bronchial asthma. J Allergy Clin Immunol 2010; 125(3): 752-4.
  11. Gudbjartsson DF, Bjornsdottir US, Halapi E, Helgadottir A, Sulem P, Jonsdottir GM, et al. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet 2009; 41(3): 342-7.
  12. Zhang Y, Moffatt MF, Cookson WO. Genetic and genomic approaches to asthma: new insights for the origins. Curr Opin Pulm Med 2012; 18(1): 6-13.
  13. Grotenboer NS, Ketelaar ME, Koppelman GH, Nawijn MC. Decoding asthma: translating genetic variation in IL33 and IL1RL1 into disease pathophysiology. J Allergy Clin Immunol 2013; 131(3): 856-65.
  14. Shimizu M, Matsuda A, Yanagisawa K, Hirota T, Akahoshi M, Inomata N, et al. Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis. Hum Mol Genet 2005; 14(19): 2919-27.
  15. Lingel A, Weiss TM, Niebuhr M, Pan B, Appleton BA, Wiesmann C, et al. Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes. Structure 2009; 17(10): 1398-410.
  16. Liew FY, Pitman NI, McInnes IB. Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 2010; 10(2): 103-10.
  17. Saadatnia M, Etemadifar M, Maghzi AH. Multiple sclerosis in Isfahan, Iran. Int Rev Neurobiol 2007; 79: 357-75.
  18. Lassmann H. What drives disease in multiple sclerosis: Inflammation or neurodegeneration? Clin Exp Neuroimmunol 2010; 1(1): 2-11.
  19. Oksenberg JR, Baranzini SE. Multiple sclerosis genetics--is the glass half full, or half empty? Nat Rev Neurol 2010; 6(8): 429-37.
  20. Hudson CA, Christophi GP, Gruber RC, Wilmore JR, Lawrence DA, Massa PT. Induction of IL-33 expression and activity in central nervous system glia. J Leukoc Biol 2008; 84(3): 631-43.
  21. Christophi GP, Gruber RC, Panos M, Christophi RL, Jubelt B, Massa PT. Interleukin-33 upregulation in peripheral leukocytes and CNS of multiple sclerosis patients. Clin Immunol 2012; 142(3): 308-19.
  22. Jiang HR, Milovanovic M, Allan D, Niedbala W, Besnard AG, Fukada SY, et al. IL-33 attenuates EAE by suppressing IL-17 and IFN-gamma production and inducing alternatively activated macrophages. Eur J Immunol 2012; 42(7): 1804-14.
  23. Oboki K, Ohno T, Kajiwara N, Saito H, Nakae S. IL-33 and IL-33 receptors in host defense and diseases. Allergol Int 2010; 59(2): 143-60.
  24. Christophi GP, Panos M, Hudson CA, Tsikkou C, Mihai C, Mejico LJ, et al. Interferon-beta treatment in multiple sclerosis attenuates inflammatory gene expression through inducible activity of the phosphatase SHP-1.Clin Immunol 2009; 133(1): 27-44.
  25. Christophi GP, Hudson CA, Panos M, Gruber RC, Massa PT. Modulation of macrophage infiltration and inflammatory activity by the phosphatase SHP-1 in virus-induced demyelinating disease. J Virol 2009; 83(2): 522-39.
  26. Yasuoka S, Kawanokuchi J, Parajuli B, Jin S, Doi Y, Noda M, et al. Production and functions of IL-33 in the central nervous system. Brain Res 2011; 1385: 8-17.
  27. Sayed BA, Walker ME, Brown MA. Cutting edge: mast cells regulate disease severity in a relapsing-remitting model of multiple sclerosis. J Immunol 2011; 186(6): 3294-8.
  28. Iikura M, Suto H, Kajiwara N, Oboki K, Ohno T, Okayama Y, et al. IL-33 can promote survival, adhesion and cytokine production in human mast cells. Lab Invest 2007; 87(10): 971-8.
  29. Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011; 476(7359): 214-9.
  30. Beecham AH, Patsopoulos NA, Xifara DK, Davis MF, Kemppinen A, Cotsapas C, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 2013; 45(11): 1353-60.
  31. Gregory AP, Dendrou CA, Attfield KE, Haghikia A, Xifara DK, Butter F, et al. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature 2012; 488(7412): 508-11.
Journal of Isfahan Medical School
Volume 33, Issue 361 - Serial Number 361
November and December 2016
Pages 2092-2101

  • Receive Date 23 August 2015
  • Accept Date 06 April 2022