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Expression and implication of toll-like receptors TLR2, TLR4 and TLR9 in colonic mucosa of patients with ulcerative colitis

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Summary

Toll-like receptors (TLRs) family may play important roles in inflammatory bowel disease. This study examined the expression of TLR2, TLR4 and TLR9 in the colonic tissues of patients with ulcerative colitis (UC) and explored their roles in the pathogenesis of UC. Colonic biopsies were taken from the colon of 30 patients with mild or moderate UC (at active phase) and 10 healthy controls during colonoscopy. TLR2, TLR4 and TLR9 protein expression levels were immunohistochemically detected. The mRNA expression levels of TLR2, TLR4 and TLR9 were assessed by reverse transcription polymerase chain reaction (RT-PCR). The disease activity index (DAI), colonoscopic and histologic grades and fecal microbial flora were determined. Histological examination showed that the intestinal mucous membrane of UC patients underwent acute inflammation changes. Immunohistochemistry exhibited that the expression levels of TLR2, TLR4 and TLR9 in colon epithelia and inflammatory cells were higher in UC patients than in control group (P<0.01). The mRNA expression levels of TLR2, TLR4 and TLR9 were increased in UC patients but were not detected in the normal controls. Expression levels of TLR2, TLR4 and TLR9 were positively correlated, and bore close correlation with DAI, colonoscopic and histologic grades and fecal microbial flora. An important mechanism of UC might be that abnormal activation of mucosal immunity by intestinal dysbacteriosis caused dysregulation of TLRS that mediates innate immunity.

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References

  1. Podolsky DK. Inflammatory bowel disease. N Engl J Med, 2002, 347(6):417–429

    Article  PubMed  CAS  Google Scholar 

  2. Chow DK, Leong RW, Tsoi KK, et al. Long-term follow-up of ulcerative colitis in the Chinese population. Am J Gastroenterol, 2009, 104(3):647–654

    Article  PubMed  Google Scholar 

  3. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature, 2007, 448(7152): 427–434

    Article  PubMed  CAS  Google Scholar 

  4. Drexler SK, Foxwell BM. The role of toll-like receptors in chronic inflammation. Int J Biochem Cell Biol, 2010, 42(4):506–518

    Article  PubMed  CAS  Google Scholar 

  5. Abreu MT. Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat Rev Immunol, 2010, 10(2):131–144

    Article  PubMed  CAS  Google Scholar 

  6. Akira S, Takeda K. Toll-like receptor signaling. Nat Rev Immunol, 2004, 4(7):499–511

    Article  PubMed  CAS  Google Scholar 

  7. The Chinese medical association digestion of neurology, inflammatory bowel disease group. To standardize the diagnosis and treatment of inflammatory bowel disease in China consensus opinion (JiNan). Chin J Dig (Chinese), 2007, 27(8):545–550

    Google Scholar 

  8. Kornbluth A, Sachar DB. Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol, 2004, 99(7):1371–1385

    Article  PubMed  Google Scholar 

  9. Tan Y, Zou KF, Yang T, et al. Clinical effect of microecologic pharmaceutical in ulcerative colitis. Chin J Dig Endosc (Chinese), 2008, 25(2):77–81

    CAS  Google Scholar 

  10. Zhong YQ, Zhu ZH, Chen WX, et al. Endoscopic characteristics of active ulcerative colitis and its relationship with clinical features. Chin J Endoscopy (Chinese), 2000, 6(4):7–8

    Google Scholar 

  11. Pullan RD, Rhodes J, Ganesh S, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med, 1994, 330(12):811–815

    Article  PubMed  CAS  Google Scholar 

  12. Moynagh PN. TLR signalling and activation of IRFs: revisiting old friends from the NF-kappaB pathway. Trends Immunol, 2005, 26(9):469–476

    Article  PubMed  CAS  Google Scholar 

  13. Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proreins linking innate and acquired immunity. Nat Immunol, 2001, 2(8):675–68

    Article  PubMed  CAS  Google Scholar 

  14. Yoshimura A, Lien E, Ingalls RR, et al. Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J Immuno, 1999, 163(1):1–5

    CAS  Google Scholar 

  15. Ulevitch RJ. Toll gates for pathogen selection. Nature, 1999, 40l(6755):755–756

    Article  Google Scholar 

  16. Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Imnlunol, 2002, 20:709–760

    Article  CAS  Google Scholar 

  17. Ma YQ, Li GF. 102 CpG—the immunology function of DNA and its application. Foreign Med Sci (Chinese), 2003, 26(06):318–321

    Google Scholar 

  18. Xun N, Ouyang Q, Yu ZH, et al. Toll-like receptor 4, CD14 and nuclear factor-κB in the expression and clinical significance of ulcerative colitis. Chin J Dig (Chinese), 2005, 25(7):433–434

    Google Scholar 

  19. Gan HT, Ouyang Q, Jia DQ, et al. Activation of nuclear factor-?B and its relationship with cytokine gene expression in colonic mucosa of ulcerative colitis patients. Chin J Inter Med (Chinese), 2002, 41(4): 252–255

    CAS  Google Scholar 

  20. Sanor RB. Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol, 2006, 3(7):390–407

    Article  Google Scholar 

  21. Cario E, Podolsky DK. Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun, 2000, 68(12):7010–7017

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Chen X, Ouyang Q, Zhang WY. Expressions of TLR4 and HBD2 in colonic intestinal epithelium of ulcerative colitis. Chin J Gastroenterol Hepatol (Chinese), 2010, 19(5):385–389

    Google Scholar 

  23. Lenoir C, Sapin C, Broquet AH, et al. MD-2 controls bacterial lipopolysaccharide hyporesponsiveness in human intestinal epitllelial cells. Life Sci, 2008, 82(9–10):519–528

    Article  PubMed  CAS  Google Scholar 

  24. Abreu MT, Vora P, Faure E, et al. Decreased expression of Toll-like receptor-4 and MD-2 Correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. J Immunol, 2001, 167(3):1609–1616

    Article  PubMed  CAS  Google Scholar 

  25. Bocker U, Yezerky O, Feick P, et al. Responsiveness of intestinal epithelial cell lines to lipopolysaccharide is correlated with toll-like receptor 4 but not toll-like receptor 2 or CDl4 expression. Int J Colorectal Dis, 2003, 18(1): 25–32

    Article  PubMed  Google Scholar 

  26. Sánchez-Muñoz F, Fonseca-Camarillo G, Villeda-Ramírez MA, et al. Transcript levels of Toll-like receptors 5, 8 and 9 correlate with inflammatory activity in ulcerative colitis. BMC Gastroenterol, 2011, 11:138

    Article  PubMed  PubMed Central  Google Scholar 

  27. Hall JA, Bouladoux N, Sun CM, et al. Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity, 2008, 29(4):637–649

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Ewaschuk JB, Backer JL, Churchill TA, et al. Surface expression of Toll-like receptor 9 is upregulated on intestinal epithelial cells in response to pathogenic bacterial DNA. Infect Immun, 2007, 75(5):2572–2579

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Fuse K, Katakura K, Sakamoto N, et al. Toll-like receptor 9 gene mutations and polymorphisms in Japanese ulcerative colitis patients. World J Gastroenterol, 2010, 16(46):5815–5821

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. Lange NE, Zhou X, Lasky-Su J, et al. Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes. BMC Med Genet, 2011, 12:26

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Chen S, Zou KF, Yang T, et al. Expression and signficance of Toll-like receptor (TLR)2, TLR4 and TLR9 in colonic mucosa of rat model with induced colitis. Chin J Gastroenterol (Chinese), 2007, 12(6):339–343

    Google Scholar 

Download references

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Correspondence to Kai-fang Zou  (邹开芳).

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This project was supported by the National Natural Science Foundation of China (No. 81170361).

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Tan, Y., Zou, Kf., Qian, W. et al. Expression and implication of toll-like receptors TLR2, TLR4 and TLR9 in colonic mucosa of patients with ulcerative colitis. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 785–790 (2014). https://doi.org/10.1007/s11596-014-1353-6

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  • DOI: https://doi.org/10.1007/s11596-014-1353-6

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