Research Article
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Year 2025, Volume: 15 Issue: 3, 217 - 224, 31.12.2025
https://doi.org/10.26650/experimed.1651136

Abstract

References

  • 1. Gül A. Pathogenesis of Behçet’s disease: Autoinflammatory features and beyond. Vol. 37, Seminars in Immunopathology. Springer Verlag; 2015. p. 413–8.
  • 2. Gul A, Inanc M, Ocal L, Aral O, Konice M. Familial aggregation of Behçet’s disease in Turkey. Ann Rheum Dis 2000; 59(8): 622–5.
  • 3. Takeuchi M, Kastner DL, Remmers EF. The immunogenetics of Behçet’s disease: A comprehensive review. J Autoimmun 2015; 64: 137.
  • 4. Deng Y, Zhu W, Zhou X. Immune regulatory genes are major genetic factors to Behcet Disease: systematic review. Open Rheumatol J 2018; 12(1): 70.
  • 5. Giza M, Koftori D, Chen L, Bowness P. Is Behçet’s disease a ‘class 1‐opathy’? The role of HLA‐B*51 in the pathogenesis of Behçet’s disease. Clin Exp Immunol 2018; 191(1): 11.
  • 6. Gül A. Behçet's disease as an autoinflammatory disorder. Curr Drug Targets Inflamm Allergy 2005; 4(1): 81-3.
  • 7. van der Houwen TB, van Hagen PM, van Laar JAM. Immunopathogenesis of Behçet’s disease and treatment modalities. Semin Arthritis Rheum 2022; 52: 151956.
  • 8. Le Joncour A, Cacoub P, Boulaftali Y, Saadoun D. Neutrophil, NETs and Behçet’s disease: A review. Clin Immunol 2023; 250: 109318.
  • 9. Neves FS, Spiller F. Possible mechanisms of neutrophil activation in Behçet’s disease. Int Immunopharmacol 2013; 17(4): 1206–10.
  • 10. Nielsen MC, Andersen MN, Møller HJ. Monocyte isolation techniques significantly impact the phenotype of both isolated monocytes and derived macrophages in vitro. Immunology 2020; 159(1): 63–74.
  • 11. Zhou L, Somasundaram R, Nederhof RF, Dijkstra G, Faber KN, Peppelenbosch MP, et al. Impact of human granulocyte and monocyte isolation procedures on functional studies. Clin Vaccine Immunol 2012; 19(7): 1065-74.
  • 12. Zheng W, Wang X, Liu J, Yu X, Li L, Wang H, et al. Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet’s disease. Proc Natl Acad Sci U S A 2022; 119(26): e2204289119.
  • 13. Tong B, Liu X, Xiao J, Su G. Immunopathogenesis of Behcet’s disease. Front Immunol 2019; 10(MAR): 435349.
  • 14. 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(7): 860-4.
  • 15. 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(2): 124–9.
  • 16. Alayli G, Aydin F, Çoban AY, SüllüY. Y, Cantürk F, Bek Y, et al. T helper 1 type cytokines polymorphisms: Association with susceptibility to Behçet’s disease. Clin Rheumatol 2007; 26(8): 1299–305.
  • 17. Özçimen AA, Dilek K, Bingöl Ü, Saricaoǧlu H, Sarandöl A, Taşkapilioǧlu Ö, et al. IL-1 cluster gene polymorphisms in Turkish patients with Behçet’s disease. Int J Immunogenet 2011; 38(4): 295–301.
  • 18. Özkan Ü, Ulutaş F, Tepeli E, Çobankara V. Interleukin-1 gene (IL-1) polymorphism in patients with Behçet’s Disease, and its relationship with disease manifestations. Eur J Inflamm 2022; 20: 1-6.
  • 19. Takeuchi M, Mizuki N, Meguro A, Ombrello MJ, Kirino Y, Satorius C, et al. Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet’s disease susceptibility. Nat Genet 2017; 49(3): 438.
  • 20. Disease ISG for B. Criteria for diagnosis of Behcet’s disease. Lancet 1990; 335(8697): 1078–80.
  • 21. Shamaa OR, Mitra S, Gavrilin MA, Wewers MD. Monocyte caspase-1 is released in a stable, active high molecular weight complex distinct from the unstable cell lysate-activated caspase-1. PLoS One 2015; 10(11): e0142203.
  • 22. Rossol M, Heine H, Meusch U, Quandt D, Klein C, Sweet MJ, et al. LPS-induced cytokine production in human monocytes and macrophages. Crit Rev Immunol 2011; 31(5): 379–446.
  • 23. Rincón E, Rocha-Gregg BL, Collins SR. A map of gene expression in neutrophillike cell lines. BMC Genomics 2018; 19(1): 573.
  • 24. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using realtime quantitative PCR and the 2-ΔΔCT method. Methods 2001; 25(4): 402–8.
  • 25. Eksioglu-Demiralp E, Direskeneli H, Kibaroglu A, Yavuz S, Ergun T, Akoglu T. Neutrophil activation in Behçet’s disease. Clin Exp Rheumatol 2001; 19(5 Suppl 24): S19-24.
  • 26. Neves FS, Carrasco S, Goldenstein-Schainberg C, Gonçalves CR, De Mello SBV. Neutrophil hyperchemotaxis in Behçet’s disease: A possible role for monocytes orchestrating bacterial-induced innate immune responses. Clin Rheumatol 2009; 28(12): 1403–10.
  • 27. McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GRS, Thormann A, et al. The ensembl variant effect predictor. Genome Biol 2016; 17(1): 122.
  • 28. Gabay C, Lamacchia C, Palmer G. IL-1 pathways in inflammation and human diseases. Nat Rev Rheum 2010; 6(4): 232–41.
  • 29. Dinarello CA. Interleukin-1 and Interleukin-1 Antagonism. Blood 1991; 77(8): 1627-52.
  • 30. Shi L, Song L, Maurer K, Dou Y, Patel VR, Su C, et al. IL-1 transcriptional responses to lipopolysaccharides are regulated by a complex of RNA binding proteins. J Immunol 2020; 204(5): 1334–44.

Cell-Based Investigation of the Association of rs4402765 Variant with IL1A and IL1B Genes in Behçet's Disease

Year 2025, Volume: 15 Issue: 3, 217 - 224, 31.12.2025
https://doi.org/10.26650/experimed.1651136

Abstract

Objective: In this study, we aimed to investigate the IL1A and IL1B mRNA expression profiles in association with the rs4402765 variant in monocytes and neutrophils to explore its role in the pathogenesis of Behçet’s disease (BD).
Materials and Methods: Monocytes and neutrophils were isolated from peripheral blood samples obtained from 15 healthy Turkish participants and genotyped for rs4402765. THP-1 and HL-60 cell lines were used as controls to determine the doses and incubation times of the lipopolysaccharide (LPS) and aluminum hydroxide (alum) triggers. Isolated cells were stimulated with LPS and alum. IL1A and IL1B mRNA expression levels were analysed using by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
Results: In monocytes stimulated with LPS for 8 h, the samples with the heterozygous rs4402765 genotype showed higher IL1B expression compared with the homozygous risk allele (CC) (p=0.016), but there was no statistically significant difference after 24 h of incubation (p=0.852). Increased IL1A expression was observed in neutrophils with the risk allele (CC) compared with the protective allele (GG) following LPS stimulation (p=0.002).
Conclusion: This study provides additional information about the functional effects of the rs4402765 variant in the IL-1 gene cluster, which may result in different expression profiles in monocytes and neutrophils, and the variability of cell-dependent expression warrants further studies.

Ethical Statement

Ethics committee approval was received for this study from the Istanbul University, Istanbul Medical Faculty Clinical Research Ethics Committee (dated 24.03.2021; Cert No. 148703).

References

  • 1. Gül A. Pathogenesis of Behçet’s disease: Autoinflammatory features and beyond. Vol. 37, Seminars in Immunopathology. Springer Verlag; 2015. p. 413–8.
  • 2. Gul A, Inanc M, Ocal L, Aral O, Konice M. Familial aggregation of Behçet’s disease in Turkey. Ann Rheum Dis 2000; 59(8): 622–5.
  • 3. Takeuchi M, Kastner DL, Remmers EF. The immunogenetics of Behçet’s disease: A comprehensive review. J Autoimmun 2015; 64: 137.
  • 4. Deng Y, Zhu W, Zhou X. Immune regulatory genes are major genetic factors to Behcet Disease: systematic review. Open Rheumatol J 2018; 12(1): 70.
  • 5. Giza M, Koftori D, Chen L, Bowness P. Is Behçet’s disease a ‘class 1‐opathy’? The role of HLA‐B*51 in the pathogenesis of Behçet’s disease. Clin Exp Immunol 2018; 191(1): 11.
  • 6. Gül A. Behçet's disease as an autoinflammatory disorder. Curr Drug Targets Inflamm Allergy 2005; 4(1): 81-3.
  • 7. van der Houwen TB, van Hagen PM, van Laar JAM. Immunopathogenesis of Behçet’s disease and treatment modalities. Semin Arthritis Rheum 2022; 52: 151956.
  • 8. Le Joncour A, Cacoub P, Boulaftali Y, Saadoun D. Neutrophil, NETs and Behçet’s disease: A review. Clin Immunol 2023; 250: 109318.
  • 9. Neves FS, Spiller F. Possible mechanisms of neutrophil activation in Behçet’s disease. Int Immunopharmacol 2013; 17(4): 1206–10.
  • 10. Nielsen MC, Andersen MN, Møller HJ. Monocyte isolation techniques significantly impact the phenotype of both isolated monocytes and derived macrophages in vitro. Immunology 2020; 159(1): 63–74.
  • 11. Zhou L, Somasundaram R, Nederhof RF, Dijkstra G, Faber KN, Peppelenbosch MP, et al. Impact of human granulocyte and monocyte isolation procedures on functional studies. Clin Vaccine Immunol 2012; 19(7): 1065-74.
  • 12. Zheng W, Wang X, Liu J, Yu X, Li L, Wang H, et al. Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet’s disease. Proc Natl Acad Sci U S A 2022; 119(26): e2204289119.
  • 13. Tong B, Liu X, Xiao J, Su G. Immunopathogenesis of Behcet’s disease. Front Immunol 2019; 10(MAR): 435349.
  • 14. 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(7): 860-4.
  • 15. 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(2): 124–9.
  • 16. Alayli G, Aydin F, Çoban AY, SüllüY. Y, Cantürk F, Bek Y, et al. T helper 1 type cytokines polymorphisms: Association with susceptibility to Behçet’s disease. Clin Rheumatol 2007; 26(8): 1299–305.
  • 17. Özçimen AA, Dilek K, Bingöl Ü, Saricaoǧlu H, Sarandöl A, Taşkapilioǧlu Ö, et al. IL-1 cluster gene polymorphisms in Turkish patients with Behçet’s disease. Int J Immunogenet 2011; 38(4): 295–301.
  • 18. Özkan Ü, Ulutaş F, Tepeli E, Çobankara V. Interleukin-1 gene (IL-1) polymorphism in patients with Behçet’s Disease, and its relationship with disease manifestations. Eur J Inflamm 2022; 20: 1-6.
  • 19. Takeuchi M, Mizuki N, Meguro A, Ombrello MJ, Kirino Y, Satorius C, et al. Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet’s disease susceptibility. Nat Genet 2017; 49(3): 438.
  • 20. Disease ISG for B. Criteria for diagnosis of Behcet’s disease. Lancet 1990; 335(8697): 1078–80.
  • 21. Shamaa OR, Mitra S, Gavrilin MA, Wewers MD. Monocyte caspase-1 is released in a stable, active high molecular weight complex distinct from the unstable cell lysate-activated caspase-1. PLoS One 2015; 10(11): e0142203.
  • 22. Rossol M, Heine H, Meusch U, Quandt D, Klein C, Sweet MJ, et al. LPS-induced cytokine production in human monocytes and macrophages. Crit Rev Immunol 2011; 31(5): 379–446.
  • 23. Rincón E, Rocha-Gregg BL, Collins SR. A map of gene expression in neutrophillike cell lines. BMC Genomics 2018; 19(1): 573.
  • 24. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using realtime quantitative PCR and the 2-ΔΔCT method. Methods 2001; 25(4): 402–8.
  • 25. Eksioglu-Demiralp E, Direskeneli H, Kibaroglu A, Yavuz S, Ergun T, Akoglu T. Neutrophil activation in Behçet’s disease. Clin Exp Rheumatol 2001; 19(5 Suppl 24): S19-24.
  • 26. Neves FS, Carrasco S, Goldenstein-Schainberg C, Gonçalves CR, De Mello SBV. Neutrophil hyperchemotaxis in Behçet’s disease: A possible role for monocytes orchestrating bacterial-induced innate immune responses. Clin Rheumatol 2009; 28(12): 1403–10.
  • 27. McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GRS, Thormann A, et al. The ensembl variant effect predictor. Genome Biol 2016; 17(1): 122.
  • 28. Gabay C, Lamacchia C, Palmer G. IL-1 pathways in inflammation and human diseases. Nat Rev Rheum 2010; 6(4): 232–41.
  • 29. Dinarello CA. Interleukin-1 and Interleukin-1 Antagonism. Blood 1991; 77(8): 1627-52.
  • 30. Shi L, Song L, Maurer K, Dou Y, Patel VR, Su C, et al. IL-1 transcriptional responses to lipopolysaccharides are regulated by a complex of RNA binding proteins. J Immunol 2020; 204(5): 1334–44.
There are 30 citations in total.

Details

Primary Language English
Subjects Genetics (Other)
Journal Section Research Article
Authors

Büneyan Tüzün 0000-0003-1032-1337

İrem Coşkuntan 0000-0003-0581-5295

Burcu Salman Yaylaz 0000-0002-9144-3899

Mehmet Güven Günver 0000-0002-4628-8391

Neslihan Abacı 0000-0002-9962-4010

Ahmet Gül 0000-0001-8219-3720

Submission Date March 6, 2025
Acceptance Date July 28, 2025
Publication Date December 31, 2025
Published in Issue Year 2025 Volume: 15 Issue: 3

Cite

Vancouver Tüzün B, Coşkuntan İ, Salman Yaylaz B, Günver MG, Abacı N, Gül A. Cell-Based Investigation of the Association of rs4402765 Variant with IL1A and IL1B Genes in Behçet’s Disease. Experimed. 2025;15(3):217-24.