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Investigation of Interleukin-10 Promoter Polymorphisms and Interleukin-10 Levels in Children with Irritable Bowel Syndrome

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Background/Aims: The aim of this study was to investigate whether genetic variations at positions -1082, -819, and -592 in the interleukin (IL)-10 promoter affect IL-10 production in children with irritable bowel syndrome (IBS). Methods:Ninety-four children with IBS and 102 children as healthy controls (HCs) were enrolled. Genomic DNA was extracted,and IL-10 -1082, -819, and -592 polymorphisms were detected by direct sequencing from all participants. Peripheral blood mononuclear cells (PBMCs) from 46 IBS children and 38 HCs were isolated and cultured with and without 5 ng/mL Escherichia coli lipopolysaccharide (LPS). IL-10 levels in the culture supernatants were measured by enzyme-linked immunosorbent assay. Results: There were no significant differences in the distribution of IL-10 -1082, -819, and -592polymorphisms or in the allele and haplotype frequencies between IBS children and HCs. PBMCs from children with IBS had significantly lower IL-10 levels after LPS stimulation than PBMCs from HCs (p=0.011); however, LPS-induced IL-10levels in PBMCs with different genotypes of -819 and -592polymorphisms were not significantly different between IBS patients and HCs. Conclusions: Although significantly lower LPS-induced IL-10 production by PBMCs was noted, it is unlikely that IL-10 production was fully genetically determined in our IBS children. ClinicalTrials.gov identifier: NCT01131442

Abstract

Background/Aims: The aim of this study was to investigate whether genetic variations at positions -1082, -819, and -592 in the interleukin (IL)-10 promoter affect IL-10 production in children with irritable bowel syndrome (IBS). Methods:Ninety-four children with IBS and 102 children as healthy controls (HCs) were enrolled. Genomic DNA was extracted,and IL-10 -1082, -819, and -592 polymorphisms were detected by direct sequencing from all participants. Peripheral blood mononuclear cells (PBMCs) from 46 IBS children and 38 HCs were isolated and cultured with and without 5 ng/mL Escherichia coli lipopolysaccharide (LPS). IL-10 levels in the culture supernatants were measured by enzyme-linked immunosorbent assay. Results: There were no significant differences in the distribution of IL-10 -1082, -819, and -592polymorphisms or in the allele and haplotype frequencies between IBS children and HCs. PBMCs from children with IBS had significantly lower IL-10 levels after LPS stimulation than PBMCs from HCs (p=0.011); however, LPS-induced IL-10levels in PBMCs with different genotypes of -819 and -592polymorphisms were not significantly different between IBS patients and HCs. Conclusions: Although significantly lower LPS-induced IL-10 production by PBMCs was noted, it is unlikely that IL-10 production was fully genetically determined in our IBS children. ClinicalTrials.gov identifier: NCT01131442

참고문헌 (40)

  1. Wyllie R, "Recurrent abdominal pain of childhood, In Nelson textbook of pediatrics. 18th ed", pp.1627~ (2007), Saunders
  2. Song GH, "Cortical effects of anticipation and endogenous modulation of visceral pain assessed by functional brain MRI in irritable bowel syndrome patients and healthy controls", Pain, 126, pp.79~90 (2006)
  3. Bouman A, "Sex hormones and the immune response in humans", Hum Reprod Update, 11, pp.411~423 (2005)
  4. Locke GR 3rd, "Familial association in adults with functional gastrointestinal disorders", Mayo Clin Proc, 75, pp.907~912 (2000)
  5. Morris-Yates A, "Evidence of a genetic contribution to functional bowel disorder", Am J Gastroenterol, 93, pp.1311~1317 (1998)
  6. Solmaz M, "Psychological factors in the irritable bowel syndrome", Eur J Med Res, 8, pp.549~556 (2003)
  7. Koloski NA, "A history of abuse in community subjects with irritable bowel syndrome and functional dyspepsia: the role of other psychosocial variables", Digestion, 72, pp.86~96 (2005)
  8. Spiller R, "Postinfectious irritable bowel syndrome", Gastroenterology, 136, pp.1979~1988 (2009)
  9. Dinan TG, "Enhanced cholinergic-mediated increase in the pro-inflammatory cytokine IL-6 in irritable bowel syndrome: role of muscarinic receptors", Am J Gastroenterol, 103, pp.2570~2576 (2008)
  10. Collins SM, "Dysregulation of peripheral cytokine production in irritable bowel syndrome", Am J Gastroenterol, 100, pp.2517~2518 (2005)
  11. Macsharry J, "Mucosal cytokine imbalance in irritable bowel syndrome", Scand J Gastroenterol, 43, pp.1467~1476 (2008)
  12. Bashashati M, "Cytokines and irritable bowel syndrome: where do we stand?", Cytokine, 57, pp.201~209 (2012)
  13. Ortiz-Lucas M, "Irritable bowel syndrome immune hypothesis. Part two: the role of cytokines", Rev Esp Enferm Dig, 102, pp.711~717 (2010)
  14. Liebregts T, "Immune activation in patients with irritable bowel syndrome", Gastroenterology, 132, pp.913~920 (2007)
  15. Hua MC, "Decreased interleukin-10 secretion by peripheral blood mononuclear cells in children with irritable bowel syndrome", J Pediatr Gastroenterol Nutr, 52, pp.376~381 (2011)
  16. Gonsalkorale WM, "Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component?", Gut, 52, pp.91~93 (2003)
  17. van der Veek PP, "Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome", Am J Gastroenterol, 100, pp.2510~2516 (2005)
  18. Mosmann TR, "Properties and functions of interleukin-10", Adv Immunol, 56, pp.1~26 (1994)
  19. Perrey C, "Genotyping for polymorphisms in interferon-gamma, interleukin-10, transforming growth factor-beta 1 and tumour necrosis factor-alpha genes: a technical report", Transpl Immunol, 6, pp.193~197 (1998)
  20. Eskdale J, "Microsatellite alleles and single nucleotide polymorphisms (SNP) combine to form four major haplotype families at the human interleukin-10 (IL-10) locus", Genes Immun, 1, pp.151~155 (1999)
  21. Thompson WG, "Functional bowel disorders and functional abdominal pain", Gut, (45 Suppl 2), pp.II43~II47 (1999)
  22. Longstreth GF, "Functional bowel disorders", Gastroenterology, 130, pp.1480~1491 (2006)
  23. Park MI, "Genetics and genotypes in irritable bowel syndrome: implications for diagnosis and treatment", Gastroenterol Clin North Am, 34, pp.305~317 (2005)
  24. Barkhordari E, "T-helper 1, T-helper 2, and T-regulatory cytokines gene polymorphisms in irritable bowel syndrome", Inflammation, 33, pp.281~286 (2010)
  25. Sartor RB, "Cytokines in intestinal inflammation: pathophysiological and clinical considerations", Gastroenterology, 106, pp.533~539 (1994)
  26. Drossman DA, "AGA technical review on irritable bowel syndrome", Gastroenterology, 123, pp.2108~2131 (2002)
  27. O’Mahony L, "Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles", Gastroenterology, 128, pp.541~551 (2005)
  28. Mocellin S, "The dual role of IL-10", Trends Immunol, 24, pp.36~43 (2003)
  29. Kindt S, "Immune dysfunction in patients with functional gastrointestinal disorders", Neurogastroenterol Motil, 21, pp.389~398 (2009)
  30. Windle HJ, "Human peripheral and gastric lymphocyte responses to Helicobacter pylori NapA and AphC differ in infected and uninfected individuals", Gut, 54, pp.25~32 (2005)
  31. Birkholz S, "Immunological activity of lipopolysaccharide of Helicobacter pylori on human peripheral mononuclear blood cells in comparison to lipopolysaccharides of other intestinal bacteria", FEMS Immunol Med Microbiol, 6, pp.317~324 (1993)
  32. Sperber K, "Cytokine secretion induced by superantigens in peripheral blood mononuclear cells, lamina propria lymphocytes, and intraepithelial lymphocytes", Clin Diagn Lab Immunol, 2, pp.473~477 (1995)
  33. Turner DM, "An investigation of polymorphism in the interleukin-10 gene promoter", Eur J Immunogenet, 24, pp.1~8 (1997)
  34. Koss K, "Cytokine (TNF alpha, LT alpha and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies", Genes Immun, 1, pp.185~190 (2000)
  35. Mahdaviani SA, "Proinflammatory cytokine gene polymorphisms among Iranian patients with asthma", J Clin Immunol, 29, pp.57~62 (2009)
  36. Movahedi M, "IL-10, TGF-beta, IL-2, IL-12, and IFN-gamma cytokine gene polymorphisms in asthma", J Asthma, 45, pp.790~794 (2008)
  37. Rezaei N, "Cytokine gene polymorphisms in common variable immunodeficiency", Int Arch Allergy Immunol, 150, pp.1~7 (2009)
  38. Barkhordari E, "Proinflammatory cytokine gene polymorphisms in irritable bowel syndrome", J Clin Immunol, 30, pp.74~79 (2010)
  39. Lee HJ, "G protein beta3 subunit, interleukin-10, and tumor necrosis factor-alpha gene polymorphisms in Koreans with irritable bowel syndrome", Neurogastroenterol Motil, 22, pp.758~763 (2010)
  40. Fickenscher H, "The interleukin-10 family of cytokines", Trends Immunol, 23, pp.89~96 (2002)

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