Ann Dermatol.  2015 Jun;27(3):291-297. 10.5021/ad.2015.27.3.291.

mRNA Expression Level of Interleukin Genes in the Determining Phases of Behcet's Disease

• Taheri S
• Borlu M
• Evereklioglu C
• Ozdemir SY
• Ozkul Y

• KMID: 2352500
• DOI: http://doi.org/10.5021/ad.2015.27.3.291

Abstract

BACKGROUND
Behcet's disease (BD), first described in 1937 as a triadic complex of symptoms (oral aphthae, genital ulcers, and hypopyon uveitis), is a chronic, relapsing, multisystemic idiopathic inflammatory disease.
OBJECTIVE
The objective of this study was to investigate the usability of messenger RNA (mRNA) expression of cytokine genes for following up patients with BD and also assess polymorphisms in these genes as to how they influence mRNA expression.
METHODS
This study investigated the role of the IL1A -889(C/T), IL1B -511(C/T), and IL2 -330(T/G) polymorphisms by polymerase chain reaction (PCR)-restriction fragment length polymorphisms and the expression levels of the genes by real-time PCR in BD.
RESULTS
The frequency of the IL2 -330 G allele was found to be significantly higher in patients with BD. A decreased level of IL1A gene expression was found in the patient group with clinically active BD compared to controls. Increased IL1B gene expression levels werefound in patient groups with active, inactive, or ocular BD (p<0.001). IL2 gene expression level manifested no significant change compared to controls in the patient group with clinically active BD; it increased in the groups with clinically inactive BD or ocular involvement.
CONCLUSION
IL1A, IL1B, and IL2 gene expression, and IL2 promoter polymorphisms, may be valuable markers for predicting risk in the development of BD. We believe that the results reveal the importance of achieving a better understanding of BD and the prospects of developing future therapeutic strategies.

Keyword

Behcet's disease; Cytokine; Inflammation; mRNA expression; Promoter polymorphism

MeSH Terms

Alleles
Gene Expression
Humans
Inflammation
Interleukin-2
Interleukins*
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
RNA, Messenger*
Stomatitis, Aphthous
Ulcer
Interleukin-2
Interleukins
RNA, Messenger

Figure

• 

  Fig. 1 Error bars indicating the expression distributions of IL1A, IL1B and IL2 genes among active, inactive, ocular and control groups.

Reference

1. Saleh Z, Arayssi T. Update on the therapy of Behçet disease. Ther Adv Chronic Dis. 2014; 5:112–134.

2. Ozkul Y, Evereklioglu C, Borlu M, Taheri S, Calis M, Dündar M, et al. 5,10-Methylenetetrahydrofolate reductase C677T gene polymorphism in Behcet's patients with or without ocular involvement. Br J Ophthalmol. 2005; 89:1634–1637.

3. Çölgeçen E, Özyurt K, Ferahbaş A, Borlu M, Kulluk P, Öztürk A, et al. The prevalence of Behçet's disease in a city in Central Anatolia in Turkey. Int J Dermatol. 2015; 54:286–289.

4. International Study Group for Behçet's Disease. Criteria for diagnosis of Behçet's disease. Lancet. 1990; 335:1078–1080.

5. Ozçimen AA, Dilek K, Bingöl U, Sarıcaoğlu H, Sarandöl A, Taşkapılıoğlu O, et al. IL-1 cluster gene polymorphisms in Turkish patients with Behçet's disease. Int J Immunogenet. 2011; 38:295–301.

6. El-Asrar AM, Struyf S, Kangave D, Al-Obeidan SS, Opdenakker G, Geboes K, et al. Cytokine profiles in aqueous humor of patients with different clinical entities of endogenous uveitis. Clin Immunol. 2011; 139:177–184.

7. Coskun M, Bacanli A, Sallakci N, Alpsoy E, Yavuzer U, Yegin O. Specific interleukin-1 gene polymorphisms in Turkish patients with Behçet's disease. Exp Dermatol. 2005; 14:124–129.

8. Togawa S, Joh T, Itoh M, Katsuda N, Ito H, Matsuo K, et al. Interleukin-2 gene polymorphisms associated with increased risk of gastric atrophy from Helicobacter pylori infection. Helicobacter. 2005; 10:172–178.

9. Lee EB, Kim JY, Zhao J, Park MH, Song YW. Haplotype association of IL-8 gene with Behcet's disease. Tissue Antigens. 2007; 69:128–132.

10. Karasneh J, Hajeer AH, Barrett J, Ollier WE, Thornhill M, Gul A. Association of specific interleukin 1 gene cluster polymorphisms with increased susceptibility for Behcet's disease. Rheumatology (Oxford). 2003; 42:860–864.

11. Alayli G, Aydin F, Coban AY, Süllü Y, Cantürk F, Bek Y, et al. T helper 1 type cytokines polymorphisms: association with susceptibility to Behçet's disease. Clin Rheumatol. 2007; 26:1299–1305.

12. Akman A, Sallakci N, Kacaroglu H, Tosun O, Yavuzer U, Alpsoy E, et al. Relationship between periodontal findings and the TNF-alpha Gene 1031T/C polymorphism in Turkish patients with Behçet's disease. J Eur Acad Dermatol Venereol. 2008; 22:950–957.

13. Ertenli I, Kiraz S, Calgüneri M, Celik I, Erman M, Haznedaroglu IC, et al. Synovial fluid cytokine levels in Behçet's disease. Clin Exp Rheumatol. 2001; 19:5 Suppl 24. S37–S41.

14. Düzgün N, Ayaşlioğlu E, Tutkak H, Aydintuğ OT. Cytokine inhibitors: soluble tumor necrosis factor receptor 1 and interleukin-1 receptor antagonist in Behçet's disease. Rheumatol Int. 2005; 25:1–5.

15. Pay S, Erdem H, Pekel A, Simsek I, Musabak U, Sengul A, et al. Synovial proinflammatory cytokines and their correlation with matrix metalloproteinase-3 expression in Behçet's disease. Does interleukin-1beta play a major role in Behçet's synovitis? Rheumatol Int. 2006; 26:608–613.

16. Sayinalp N, Ozcebe OI, Ozdemir O, Haznedaroğlu IC, Dündar S, Kirazli S. Cytokines in Behçet's disease. J Rheumatol. 1996; 23:321–322.

17. Evereklioglu C, Er H, Türköz Y, Cekmen M. Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet's disease. Mediators Inflamm. 2002; 11:87–93.

18. Nelson BH. IL-2, regulatory T cells, and tolerance. J Immunol. 2004; 172:3983–3988.

19. Iliopoulos AG, Tsokos GC. Immunopathogenesis and spectrum of infections in systemic lupus erythematosus. Semin Arthritis Rheum. 1996; 25:318–336.

20. Kovacs B, Vassilopoulos D, Vogelgesang SA, Tsokos GC. Defective CD3-mediated cell death in activated T cells from patients with systemic lupus erythematosus: role of decreased intracellular TNF-alpha. Clin Immunol Immunopathol. 1996; 81:293–302.

21. Shahram F, Nikoopour E, Rezaei N, Saeedfar K, Ziaei N, Davatchi F, et al. Association of interleukin-2, interleukin-4 and transforming growth factor-beta gene polymorphisms with Behcet's disease. Clin Exp Rheumatol. 2011; 29:4 Suppl 67. S28–S31.

22. Hamzaoui K, Hamzaoui A, Guemira F, Bessioud M, Hamza M, Ayed K. Cytokine profile in Behçet's disease patients. Relationship with disease activity. Scand J Rheumatol. 2002; 31:205–210.

23. Zhou ZY, Chen SL, Shen N, Lu Y. Cytokines and Behcet's disease. Autoimmun Rev. 2012; 11:699–704.

24. Hoogendoorn B, Coleman SL, Guy CA, Smith K, Bowen T, Buckland PR, et al. Functional analysis of human promoter polymorphisms. Hum Mol Genet. 2003; 12:2249–2254.