Molecular Pathogenesis of Lichen Planus
Lichen planus is a chronic mucocutaneous inflam- matory disorder of unknown etiology. The pathogenesis of lichen planus at the molecular level has not yet been known. Two hypotheses, i.e. antigen-specific versus non-specific mechanisms, are proposed in order to explain a number of experimental results that have been reported since the last decade. Antigen-specific mecha- nisms include antigen presentation and antigen-specific killing by CD8 cytotoxic T-lymphocytes, while non- specific mechanisms involve mast cell degranulation and matrix metalloproteinase activation. The final conse- quences of these two mechanisms are apparent from the histological findings of lichen planus, which include accumulation of T-lymphocytes, basement membrane disruption, and basal cell degeneration (or keratinocyte apoptosis). In addition, several lines of evidence regard- ing keratinocyte apoptosis in oral lichen planus, i.e. acti- vation of caspase-3 and cleavage of poly (ADP-ribose) polymerase, have been presented in this review article. However, additional studies are still required for a thorough understanding of the etiology and pathogenesis of lichen planus.
1. Sugerman PB, Savage NW, Walsh LJ, Zhao ZZ, Zhou XJ, Khan A, et al. The pathogenesis or oral lichen planus. Crit Rev Oral Biol Med 2002; 13: 351-367.
2. Chainani-Wu N, Silverman SJr, Lozada-Nur F, Mayer P, Watson JJ. Oral lichen planus: patient profile, disease progression and treatment responses. J Am Dent Assoc 2001; 132: 901-909.
3. Axéll T, Rundqvist L. Oral lichen planus- a demo- graphic study. Community Dent Oral Epidemiol 1987; 15: 52-56.
4. Eisen D. The evaluation of cutaneous, genital, scalp, nail, esophageal, and ocular involvement in patients with oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999; 88:431-436.
5. Zhou XJ, Sugerman PB, Savage NW, Walsh LJ. Matrix metalloproteinases and their inhibitors in oral lichen planus. J Catan Pathol 2001: 28:72-82.
6. Haapalainen T, Oksala O, Kallioinen M. Oikarinen A. Larjava H, Salo T. Destruction of the epithelial anchoring system in lichen planus. J Invest Dermatol 1995; 105: 100-103.
7. Scully C. Beyli M. Ferreiro MC, Ficarra G, Gill Y, Griffiths M. et al. Update on oral lichen planus: etiopathogenesis and management. Crit Rev Oral Biol Med 1998; 9:86-122.
8. Sugerman PB, Satterwhite K., Bigby M. Auto- cytotoxic T cell clones in lichen planus. Br J Dermatol 2000, 142:449-456.
9. Yamamoto T. Osaki T, Yoneda K, Ueta E. Cytokine production by keratinocytes and mono- nuclear infiltrates in oral lichen planus. J Oral Pathol Med 1994; 23:309-315.
10. Yamamoto T. Osaki T. Characteristic cytokines generated by keratinocytes and mononuclear infil- trates in oral lichen planus. J Invest Dermatol 1995; 104:784-788.
11. Holmstrup P, Dabelsteen E Changes in carbohy drate expression of lichen planus affected oral epithelial cell membrane. J Invest Dermanol 1979, 73:364-367.
12. Spetz AL., Strominger J, Groh-Spies V. Tcell sub- sets in normal human epidermis. Am J Pathol 1996; 149:665-74.
13. Sallusto F. Lanzavecchia A. Mackay CR. Chemo kines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses. Immunol Today 1998; 19:568-574.
14. Sugerman PB, Savage NW, Xu LJ, Walsh LJ, Seymour GJ. Heat shock protein expression in oral lichen planus. J Oral Pathol Med 1995 24:1-8.
15. Chaiyarit P. Kafrawy AH, Miles DA. Zunt St., Van Dis ML, Gregory RL Oral lichen planus, an im- munohistochemical study of heat shock proteins (HSP) and cytokeratins (CKs) and a unifying hypothesis of pathogenesis. J Oral Pathol Med 1999, 28:210-215.
16. Ahika Y. Jinhu Y, Noguchi Y. Nishimura M. Kusano K. Amaratunga P, et al. Upregulation of human beta-defensin 2 peptide expression in oral lichen planos, leukoplakia and candidiasis: an im munohistochemical study. Pathol Res Pract 2002; 198:537-542.
17. Sugerman PB, Savage NW, Seymour GJ, Walsh LI. Is there a role for tumor necrosis factor alpha (TNF-x) in oral lichen planus? J Oral Pathol Med 1996; 25-219-224.
18. Simark-Mattsson C. Bergenholtz G, Jontell M. Eklund C. Seymour GJ, Sugerman PB, et al. Distribution of interleukin-2, -4, -10, tumor necro sis factor-x and transforming growth factor-fl mRNAs in otul lichen planus. Arch Oral Biol 1999, 44:499-507.
19. Constant SL, Bottomly K. Induction of Thi and Th2 CD+ T cell responsex: the alternative approaches. Anna Rev Immunol 1997; 15:297-322.
20. Malfaii AM, Butler DM, Prusky DH, Maini RN. Brennan FM, Feldmann M. Blockade of IL-12 during the indoction of collagen-induced arthritis (CIA) markedly attenuates the severity of the arthritis. Clin Exp Immunol 1998; 111:377-383.
21. Windhagen A, Newcombe I. Dungond F. Strand C, Woodroofe MN, Cuzner Mi, et al. Expression of costimulatory molecules B7-1 (CD80), 87-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. Exp Med 1995; 182:1985- 1996.
22. Walton 13. Macey MG, Thornhill MH. Farthing PM. Intraepithelial subpopulations of T lympho- cytes and Langerhans cells in oral lichen planus. J Oral Pathol Med 1998; 27:116-123.
23. Marinkovich MP. Keene DR, Rimberg CS, Burgeson RE. Cellular origin of the dermal epidermal basement membrane. Dev Dyn 1993; 197:255-267.
24. Zhou XJ, Sugerman PB, Savage NW, Waisli L.J. Matrix metalloproteinases and their inhibitors in. oral lichen planus. J Catan Pathol 2001;28-72-82.
25. Zhao ZZ, Savage NW. Pujic 2. Walsis L. Imamo nohistochemical localization of mast cells and mast-cell-nerve interactions in oral lichen planus, Oral Dis 1997, 3:71-76.
26. Zhao ZZ, Sugerman PB, Zhou XJ, Walsh LJ, Sav age NW. Mast cell degranulation and the role of T cell RANTES in oral lichen planus. Oral Dis 2001, 7:246-251.
27. Fang KC, Raymond WW. Blount JL. Caughey GH. Dog mast cell alpha-chymase activates progelatinase B by cleaving the Phess-Glis89 and Phe91-Glu92 bonds of the catalytic domain. J Biol Chem 1997: 272-25628-25635.
28. Tomei LD, Shapins JP, Cope FO. Apoptosis in C3H/10T1/2 mouse embryonic cells: evidence for internucleosonal DNA modification in the absence of double-stranded cleavage Proc Natl Acad Sci USA 1993:90:853-857.
29. Zakeri ZF. Quglino D. Latham T. Lockoshin RA. Delayed interniclessomal DNA fragmentation in programmed cell death. FASERJ 1993, 7:470-478.