Background: Oral lichen planus (OLP) is a chronic immune-mediated inflammatory disease that usually causes oral mucosal damage. OLP has been considered to be a potentially malignant disorder associated with an increased risk for oral cancer. Trefoil factors (TFFs) are mainly synthesized by mucin-producing epithelial cells. Expression of TFFs in oral epithelia is thought to be an essential factor in protection against oral mucosal damage. However, very little is known about the connection between tissue damage of oral mucosa in OLP patients and expression of TFFs.
Objectives: To determine levels of TFF expression in oral mucosa from patients with OLP.
Methods: Tissue samples were collected from 35 patients with normal oral mucosa (controls) and 35 patients with OLP. An immunohistochemical method was used to determine the expression of the 3 TFFs (TFF1, 2, and 3) in mucosal tissues of the oral cavity.
Results:TFF2 and TFF3 expression in oral epithelia were significantly decreased in OLP patients (Mann- Whitney U test; P = 0.006, and P = 0.002, respectively). There were no significant differences in TFF1 expression between OLP patients and control subjects.
Conclusion: The present study demonstrated reduced expression of TFF2 and TFF3 in oral epithelia of OLP patients. These outcomes support our previous observations that chronic inflammation may play a major role in downregulation of TFF expression, which may be associated with oral mucosal damage in OLP patients.
1. Thim L, May FEB. Structure of mammalian trefoil factors and functional insights. Cell Mol Life Sci. 2005; 62:2956-73.
2. Kjellev S. The trefoil factor family-small peptides with multiple functionalities. Cell Mol Life Sci. 2009; 66: 1350-69.
3. Dossinger V, Kayademir T, Blin N, Gött P. Downregulation of TFF expression in gastrointestinal cell lines by cytokines and nuclear factors. Cell Physiol Biochem. 2002; 12:197-206.
4. Tebbutt NC, Giraud AS, Inglese M, Jenkins B, Waring P, Clay FJ, et al. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STATmediated trefoil gene activation in gp130 mutant mice. Nat Med. 2002; 8:1089-97.
5. Chaiyarit P, Utrawichian A, Leelayuwat C, Vatanasapt P, Chanchareonsook N, Samson MH, et al. Investigation of trefoil factor expression in saliva and oral mucosal tissues of patients with oral squamous cell carcinoma. Clin Oral Invest. 2012; 16: 1549-56.
6. Chaiyarit P, Chayasadom A, Wara-Aswapati N, Hormdee D, Sittisomwong S, Nakaresisoon S, et al. Trefoil factors in saliva and gingival tissues of patients with chronic periodontitis. J Periodontol 2012; 83:1129-38.
7. Jagla W, Wiede A, Hinz M, Dietzmann K, Gülicher D, Gerlach KL, et al. Secretion of TFF-peptides by human salivary glands. Cell Tissue Res. 1999; 298:161-6.
8. Devine DA, High AS, Owen PJ, Poulsom R, Bonass WA. Trefoil factor expression in normal and diseased human salivary glands. Hum Pathol. 2000; 31:509-15.
9. Kouznetsova I, Gerlach KL, Zahl C, Hoffmann W. Expression analysis of human salivary glands by laser microdissection: differences between submandibular and labial glands. Cell Physiol Biochem. 2010; 26:375-82.
10. Kutta H, May J, Jaehne M, Münscher A, Paulsen FP. Antimicrobial defence mechanisms of the human parotid duct. J Anat. 2006; 208:609-19.
11. Samson MH, Chaiyarit P, Nortvig H, Vestergaad EM, Ernst E, Nexø E. Trefoil factor family peptides in human saliva and in cyclical cervical mucus. Method evaluation and results on healthy individuals. Clin Chem Lab Med. 2011; 49:861-8.
12. Storesund T, Hayashi K, Kolltveit KM, Bryne M, Schenck K. Salivary trefoil factor 3 enhances migration of oral keratinocytes. Eur J Oral Sci. 2008; 116:135-40.
13. Storesund T, Schenck K, Osmundsen H, Røed A, Helgeland K, Kolltveit KM. Signal transduction and gene transcription induced by TFF3 in oral keratinocytes. Eur J Oral Sci. 2009; 117:511-7.
14. Roopashree MR, Gondhalekar RV, Shashikanth MC, George J, Thippeswamy SH, Shukla A. Pathogenesis of oral lichen planus-a review. J Oral Pathol Med. 2010; 39:729-34.
15. Lodi G, Scully C, Carrozzo M, Griffiths M, Sugerman PB, Thongprasom K. Current controversies in oral lichen planus: report of an international consensus meeting. Part 1. Viral infections and etiopathogenesis Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005; 100:40-51.
16. Chaiyarit P, Jintakanon D, Klanrit P, Siritapetawee M, Thongprasom K. Immunohistochemical analyses of surviving and heat shock protein 90 expression in patients with oral lichen planus. J.Oral Pathol.Med. 2009; 38:55-62.
17. van der Waal I. Potentially malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. Oral Oncol. 2010; 46:423-5.
18. Ergun S, Troþala SC, Warnakulasuriya S, Özel S, Önal AE, Ofluoðlu D, et al. Evaluation of oxidative stress and antioxidant profile in patients with oral lichen planus. J Oral Pathol Med. 2011; 40:286-93.
19. Chaiyarit P, Ma N, Hiraku Y, Pinlaor S, Yongvanit P, Jintakanon D, et al. Nitrative and oxidative DNA damage in oral lichen planus in relation to human oral carcinogenesis. Cancer Sci. 2005; 96:553-9.
20. Bascones-Ilandain C, Gonzalez-Moles MA, Esparza- Gomez G, Gil-Montoya JA, Bascones-Martinez A. Significance of liquefaction degeneration in oral lichen planus: a study of its relationship with apoptosis and cell cycle arrest markers. Clin Exp Dermatol. 2007; 32:556-63.
21. Hirota M, Ito T, Okudela K, Kawabe R, Yazawa T, Hayashi H, et al. Cell proliferation activity and expression of cell cycle regulatory proteins in oral lichen planus. J Oral Pathol Med. 2002; 31:204-12.
22. van der Meij EH, van der Waal I. Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications. J Oral Pathol Med. 2003; 32:507-12.
23. Gandolfo S, Richiardi L, Carrozo M, Broccoletti R, Carbone M, Pagano M, et al. Risk of squamous cell carcinoma in 402 patients with oral lichen planus: a follow-up in an Italian population. Oral Oncol. 2004; 40:77-83.
24. Thongprasom K, Luengvisut P, Wongwatanakit A, Boonjatturus C. Clinical evaluation in treatment of oral lichen planus with topical fluocinolone acetonide: a 2-year follow-up. J Oral Pathol Med. 2003; 32:315-22.
25. Verey F, Nexø E, Greenwood R, Berry M, Corfield AP. Trefoil factor family peptides are increased in the saliva of children with mucositis. Clin Chem Lab Med. 2011; 49:205105.
26. Zhou G, Xia K, Du GF, Chen XM, Xu XY, Lu R, et al. Activation of nuclear factor-kappa B correlates with tumor necrosis factor-alpha in oral lichen planus: a clinicopathologic study in atrophic-erosive and reticular form. J Oral Pathol Med. 2009; 38:559-64.
27. Vandenbroucke K, Hans W, Van Huysse J, Neirynck S, Demetter P, Remaut E, et al. Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology. 2004; 127:502-13.
28. Peterson DE, Barker NP, Akhmadullina LI, Rodionova I, Sherman NZ, Davidenko IS, et al. Phase II, randomized, double-blind, placebo-controlled study of recombinant human intestinal trefoil factor oral spray for prevention of oral mucositis in patients with colorectal cancer who are receiving fluorouracil-based chemotherapy. J Clin Oncol. 2009; 27:4333-8.
29. Perry JK, Kannan N, Grandison PM, Mitchell MD, Lobie PE. Are trefoil factors oncogenic? Trends Endocrinol Metab. 2008; 19:74-81.