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S100A Expression and Interleukin-10 Polymorphisms Are Associated with Ulcerative Colitis and Diarrhea Predominant Irritable Bowel Syndrome

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Abstract

Background

Both ulcerative colitis (UC) and diarrhea-predominant irritable bowel syndrome (IBS-D) are associated with alterations in enteric serotonin (5-HT) signaling.

Aims

The purpose of this study was to compare the rectal and sigmoid colonic mucosal expression of S100A proteins and functional polymorphisms of the 5-HT transporter (5HTT) and interleukin-10 genes in patients with IBS-D or UC with healthy controls.

Methods

mRNA expression of S100 proteins was measured in sigmoid and rectal biopsies and in rectal epithelium isolated by laser-captured microdissection. Leucocyte DNA was analyzed by PCR-based reaction fragment length polymorphisms and direct sequencing. Clinical symptoms were assessed by the self-rating depression scale and by the gastrointestinal symptom rating scale.

Results

Fifty patients with IBS-D, 56 with UC and 50 healthy controls were studied. Colonic mucosal expression of S100A8 and S100A9 in UC was significantly higher than in IBS or controls and correlated with the UC disease activity index (r = 0.65, p < 0.001). S100A10 expression in the rectal epithelium of the IBS patients was significantly higher (0.643 vs. 0.402, p = 0.01) than in controls and correlated with the SDS scores (r = 0.41, p = 0.002). The frequency of IL10-819 CC genotype was significantly higher in IBS-D (10.7 vs. 0 %, p = 0.047) and UC (16 vs. 0 %, p = 0.007) than that in controls.

Conclusion

Overexpression of S100A10 in the rectum may play a role in IBS as it is involved in modulating 5-HT1B receptors. The IL10-819 CC is a candidate genotype for both IBS and UC in Japanese.

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References

  1. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology. 2006;130:1480–1491.

    Article  PubMed  Google Scholar 

  2. Kim DY, Camilleri M. Serotonin: a mediator of the brain-gut connection. Am J Gastroenterol. 2000;95:2698–2709.

    PubMed  CAS  Google Scholar 

  3. Lucki I. The spectrum of behaviors influenced by serotonin. Biol Psychiatry. 1998;44:151–162.

    Article  PubMed  CAS  Google Scholar 

  4. Wade PR, Chen J, Jaffe B, et al. Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci. 1996;16:2352–2364.

    PubMed  CAS  Google Scholar 

  5. Torres GE, Gainetdinov RR, Caron MG. Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci. 2003;4:13–25.

    Article  PubMed  CAS  Google Scholar 

  6. Bengel D, Johren O, Andrews AM, et al. Cellular localization and expression of the serotonin transporter in mouse brain. Brain Res. 1997;778:338–345.

    Article  PubMed  CAS  Google Scholar 

  7. Ahonen A, Kyosola K, Penttila O. Enterochromaffin cells in macrophages in ulcerative colitis and irritable colon. Ann Clin Res. 1976;8:1–7.

    PubMed  CAS  Google Scholar 

  8. Capurso L, Friedmann CA. Distribution of 5-OH tryptamine (serotonin) in ulcerative colitis. Proc R Soc Med. 1970;63 Suppl:20–21.

    PubMed  CAS  Google Scholar 

  9. Kyosola K, Penttila O, Salaspuro M. Rectal mucosal adrenergic innervation and enterochromaffin cells in ulcerative colitis and irritable colon. Scand J Gastroenterol. 1977;12:363–367.

    Article  PubMed  CAS  Google Scholar 

  10. Linden DR, Chen JX, Gershon MD, et al. Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol. 2003;285:G207–G216.

    PubMed  CAS  Google Scholar 

  11. Magro F, Vieira-Coelho MA, Fraga S, et al. Impaired synthesis or cellular storage of norepinephrine, dopamine, and 5-hydroxytryptamine in human inflammatory bowel disease. Dig Dis Sci. 2002;47:216–224.

    Article  PubMed  CAS  Google Scholar 

  12. Miwa J, Echizen H, Matsueda K, et al. Patients with constipation-predominant irritable bowel syndrome (IBS) may have elevated serotonin concentrations in colonic mucosa as compared with diarrhea-predominant patients and subjects with normal bowel habits. Digestion. 2001;63:188–194.

    Article  PubMed  CAS  Google Scholar 

  13. Verity MA, Mellinkoff SM, Frankland M, et al. Serotonin content and argentaffin and Paneth cell changes in ulcerative colitis. Gastroenterology. 1962;43:24–31.

    PubMed  CAS  Google Scholar 

  14. Yeo A, Boyd P, Lumsden S, et al. Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women. Gut. 2004;53:1452–1458.

    Article  PubMed  CAS  Google Scholar 

  15. Pata C, Erdal ME, Derici E, et al. Serotonin transporter gene polymorphism in irritable bowel syndrome. Am J Gastroenterol. 2002;97:1780–1784.

    Article  PubMed  CAS  Google Scholar 

  16. Park MI, Camilleri M. Genetics and genotypes in irritable bowel syndrome: implications for diagnosis and treatment. Gastroenterol Clin North Am. 2005;34:305–317.

    Article  PubMed  Google Scholar 

  17. Camilleri M, Atanasova E, Carlson PJ, et al. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2002;123:425–432.

    Article  PubMed  CAS  Google Scholar 

  18. Heils A, Teufel A, Petri S, et al. Allelic variation of human serotonin transporter gene expression. J Neurochem. 1996;66:2621–2624.

    Article  PubMed  CAS  Google Scholar 

  19. Lesch KP, Balling U, Gross J, et al. Organization of the human serotonin transporter gene. J Neural Transm Gen Sect. 1994;95:157–162.

    Article  PubMed  CAS  Google Scholar 

  20. Offenbaecher M, Bondy B, de Jonge S, et al. Possible association of fibromyalgia with a polymorphism in the serotonin transporter gene regulatory region. Arthritis Rheum. 1999;42:2482–2488.

    Article  PubMed  CAS  Google Scholar 

  21. Ogilvie AD, Battersby S, Bubb VJ, et al. Polymorphism in serotonin transporter gene associated with susceptibility to major depression. Lancet. 1996;347:731–733.

    Article  PubMed  CAS  Google Scholar 

  22. Osher Y, Hamer D, Benjamin J. Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs. Mol Psychiatry. 2000;5:216–219.

    Article  PubMed  CAS  Google Scholar 

  23. Sperber AD, Atzmon Y, Neumann L, et al. Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications. Am J Gastroenterol. 1999;94:3541–3546.

    Article  PubMed  CAS  Google Scholar 

  24. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002;122:1140–1156.

    Article  PubMed  Google Scholar 

  25. Andersen V, Ernst A, Christensen J, et al. The polymorphism rs3024505 proximal to IL-10 is associated with risk of ulcerative colitis and Crohns disease in a Danish case-control study. BMC Med Genet. 2010;11:82.

    Article  PubMed  Google Scholar 

  26. Turner DM, Williams DM, Sankaran D, et al. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet. 1997;24:1–8.

    Article  PubMed  CAS  Google Scholar 

  27. Johne B, Fagerhol MK, Lyberg T, et al. Functional and clinical aspects of the myelomonocyte protein calprotectin. Mol Pathol. 1997;50:113–123.

    Article  PubMed  CAS  Google Scholar 

  28. Foell D, Roth J. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum. 2004;50:3762–3771.

    Article  PubMed  CAS  Google Scholar 

  29. Roth J, Vogl T, Sorg C, et al. Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. Trends Immunol. 2003;24:155–158.

    Article  PubMed  CAS  Google Scholar 

  30. Manolakis AC, Kapsoritakis AN, Tiaka EK, et al. Calprotectin, calgranulin C, and other members of the s100 protein family in inflammatory bowel disease. Dig Dis Sci. 2011;56:1601–1611.

    Article  PubMed  CAS  Google Scholar 

  31. Foell D, Wittkowski H, Roth J. Monitoring disease activity by stool analyses: from occult blood to molecular markers of intestinal inflammation and damage. Gut. 2009;58:859–868.

    Article  PubMed  CAS  Google Scholar 

  32. Foell D, Wittkowski H, Ren Z, et al. Phagocyte-specific S100 proteins are released from affected mucosa and promote immune responses during inflammatory bowel disease. J Pathol. 2008;216:183–192.

    Article  PubMed  CAS  Google Scholar 

  33. Leach ST, Yang Z, Messina I, et al. Serum and mucosal S100 proteins, calprotectin (S100A8/S100A9) and S100A12, are elevated at diagnosis in children with inflammatory bowel disease. Scand J Gastroenterol. 2007;42:1321–1331.

    Article  PubMed  CAS  Google Scholar 

  34. Vermeire S, Van Assche G, Rutgeerts P. Laboratory markers in IBD: useful, magic, or unnecessary toys? Gut. 2006;55:426–431.

    Article  PubMed  CAS  Google Scholar 

  35. Tibble JA, Sigthorsson G, Bridger S, et al. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology. 2000;119:15–22.

    Article  PubMed  CAS  Google Scholar 

  36. Tibble J, Teahon K, Thjodleifsson B, et al. A simple method for assessing intestinal inflammation in Crohn’s disease. Gut. 2000;47:506–513.

    Article  PubMed  CAS  Google Scholar 

  37. Coulie B, Tack J, Maes B, et al. Sumatriptan, a selective 5-HT1 receptor agonist, induces a lag phase for gastric emptying of liquids in humans. Am J Physiol. 1997;272:G902–G908.

    PubMed  CAS  Google Scholar 

  38. Svenningsson P, Chergui K, Rachleff I, et al. Alterations in 5-HT1B receptor function by p11 in depression-like states. Science. 2006;311:77–80.

    Article  PubMed  CAS  Google Scholar 

  39. Camilleri M, Andrews CN, Bharucha AE, et al. Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology. 2007;132:17–25.

    Article  PubMed  CAS  Google Scholar 

  40. Sutherland LR, Martin F. 5-Aminosalicylic acid enemas in treatment of distal ulcerative colitis and proctitis in Canada. Dig Dis Sci. 1987;32:64S–66S.

    Article  PubMed  CAS  Google Scholar 

  41. Gabrys JB, Peters K. Reliability, discriminant and predictive validity of the Zung Self-rating Depression Scale. Psychol Rep. 1985;57:1091–1096.

    Article  PubMed  CAS  Google Scholar 

  42. Oka T, Tamagawa Y, Hayashida S, et al. Rikkunshi-to attenuates adverse gastrointestinal symptoms induced by fluvoxamine. Biopsychosoc Med. 2007;1:21.

    Article  PubMed  Google Scholar 

  43. Svedlund J, Sjodin I, Dotevall G. GSRS—a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988;33:129–134.

    Article  PubMed  CAS  Google Scholar 

  44. Donier E, Rugiero F, Okuse K, et al. Annexin II light chain p11 promotes functional expression of acid-sensing ion channel ASIC1a. J Biol Chem. 2005;280:38666–38672.

    Article  PubMed  CAS  Google Scholar 

  45. Cervero F, Laird JM. Understanding the signaling and transmission of visceral nociceptive events. J Neurobiol. 2004;61:45–54.

    Article  PubMed  CAS  Google Scholar 

  46. Robinson MJ, Tessier P, Poulsom R, et al. The S100 family heterodimer, MRP-8/14, binds with high affinity to heparin and heparan sulfate glycosaminoglycans on endothelial cells. J Biol Chem. 2002;277:3658–3665.

    Article  PubMed  CAS  Google Scholar 

  47. Schreiber S, Heinig T, Thiele HG, et al. Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease. Gastroenterology. 1995;108:1434–1444.

    Article  PubMed  CAS  Google Scholar 

  48. Correa I, Veny M, Esteller M, et al. Defective IL-10 production in severe phenotypes of Crohn’s disease. J Leukoc Biol. 2009;85:896–903.

    Article  PubMed  CAS  Google Scholar 

  49. Tagore A, Gonsalkorale WM, Pravica V, et al. Interleukin-10 (IL-10) genotypes in inflammatory bowel disease. Tissue Antigens. 1999;54:386–390.

    Article  PubMed  CAS  Google Scholar 

  50. Gonsalkorale WM, Perrey C, Pravica V, et al. Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component? Gut. 2003;52:91–93.

    Article  PubMed  CAS  Google Scholar 

  51. Zhu H, Lei X, Liu Q, et al. Interleukin-10-1082A/G polymorphism and inflammatory bowel disease susceptibility: a meta-analysis based on 17,585 subjects. Cytokine. 2013;61:146–153.

    Article  PubMed  CAS  Google Scholar 

  52. van der Veek PP, van den Berg M, de Kroon YE, et al. Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome. Am J Gastroenterol. 2005;100:2510–2516.

    Article  PubMed  Google Scholar 

  53. Sakuyama K, Meguro A, Ota M, et al. Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients. Mol Vis. 2012;18:512–518.

    PubMed  CAS  Google Scholar 

  54. Kotani K, Shimomura T, Shimomura F, et al. A polymorphism in the serotonin transporter gene regulatory region and frequency of migraine attacks. Headache. 2002;42:893–895.

    Article  PubMed  Google Scholar 

  55. Kim WK, Kim HS, Kim WJ, et al. Serotonin transporter gene polymorphism and migraine in the Korean population. Headache. 2005;45:1056–1060.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan

    Akiko Shiotani, Yoshiki Kimura, Mnabu Ishii, Hiroshi Imamura, Ken-ichi Tarumi, Tomoari Kamada & Ken Haruma

  2. Department of Comprehensive Medicine, Kawasaki Medical School, Okayama, Japan

    Hiroaki Kusunoki

  3. Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Okayama, Japan

    Noriaki Manabe & Jiro Hata

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  1. Akiko Shiotani
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Correspondence to Akiko Shiotani.

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Shiotani, A., Kusunoki, H., Kimura, Y. et al. S100A Expression and Interleukin-10 Polymorphisms Are Associated with Ulcerative Colitis and Diarrhea Predominant Irritable Bowel Syndrome. Dig Dis Sci 58, 2314–2323 (2013). https://doi.org/10.1007/s10620-013-2677-y

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