Alcalá PD, Gómez MVM, Jurado SF

Idioma: Español
Referencias bibliográficas: 34
Paginas: 56-62
Archivo PDF: 187.67 Kb.

RESUMEN

Los receptores tipo Toll (TLRs) representan un grupo de reconocimiento de patrones moleculares ampliamente estudiados como parte esencial de la respuesta inmune innata y adaptativa, tanto en padecimientos de origen infeccioso como no infeccioso. Se han descrito aproximadamente 15 TLRs en mamíferos, de los cuales 10 se encuentran en humanos. La piel, al ser el primer órgano de defensa contra el medio externo, expresa TLRs en una gran variedad de células cutáneas, lo que favorece la respuesta inmune de esta línea de defensa. Al estudiar los TLRs, sabemos que se encuentran implicados en diversas enfermedades dermatológicas, como: acné, rosácea, psoriasis, dermatitis atópica, LES (lupus eritematoso sistémico), micosis fungoide, sífilis, lepra, Candida, piodermias, virosis cutáneas, cáncer, por mencionar algunas, lo que abre el camino para el desarrollo de nuevas líneas terapéuticas.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Miller LS, Modlin RL. Toll-like receptors in the skin. Semin Immunopathol. 2007; 29: 15-26.

2. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Toll protein signals activation of adaptative immunity. Nature. 1997; 338: 394-397.

3. Lemaitre B, Nicholas E, Michaut L et al. The dorso ventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996; 86: 973-983.

4. Kaisho T, Akira S. Toll-like receptor function and signaling. J Allergy Clin Immunol. 2006; 117: 979-987.

5. Valins W, Amini S, Berman B. The expression of Toll-like receptors in dermatological diseases and the therapeutic effect of current and newer topical Toll-like receptor modulators. J Clin Aesthet Dermatol. 2010; 3: 20-29.

6. Vanessa P, Anthony A, Toll-like receptors and dermatology, review. International Journal of Dermatology. 2009; 48: 558-570.

7. Lebre MC, van der Aar AM, van BL, van Capel TM, Schuitemaker JH, Kapsenberg ML. Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9. J Invest Dermatol. 2007; 127: 331-341.

8. Renn CN, Sanchez DJ, Ochoa MT, Legaspi AJ, Oh CK, Liu PT. TLR activation of Langerhans cell-like dendritic cells triggers an antiviral immune response. J Immunol. 2006; 177: 298-305.

9. Krutzik SR, Tan B, Li H, Ochoa MT, Liu PT, Sharfstein SE. TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. Nat Med. 2005; 11: 653-660.

10. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006; 311: 1770-1773.

11. Kulka M, Metcalfe DD. TLR3 activation inhibits human mast cell attachment to fibronectin and vitronectin. Mol Immunol. 2006; 43: 1579-1586.

12. Faure E, Equils O, Sieling PA, Thomas L, Zhang FX, Kirschning CJ. Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J Biol Chem. 2000; 275: 11058-11063.

13. Caron G, Duluc D, Fremaux I, Jeannin P, David C, Gascan H. Direct stimulation of human T cells via TLR5 and TLR7/8: flagellin and R-848 up-regulate proliferation and IFN-gamma production by memory CD4+ T cells. J Immunol. 2005; 175: 1551-1557.

14. Lau CM, Broughton C, Tabor AS, Akira S, Flavell RA, Mamula MJ. RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement. J Exp Med. 2005; 202: 1171-1177.

15. Proost P, Vynckier AK, Mahieu F, Put W, Grillet B, Struyf S, Wuyts A. Microbial Toll-like receptor ligands differentially regulate CXCL10/IP-10 expression in fibroblasts and mononuclear leukocytes in synergy with IFNgamma and provide a mechanism for enhanced synovial chemokine levels in septic arthritis. Eur J Immunol. 2003; 33: 3146-3153.

16. Creely SJ, McTernan PG, Kusminski CM, Fisher FM, Khanolkar M, Evans M. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab. 2006. DOI 10.1152/ajpendo.00302.2006

17. Liu T, Xu ZZ, Park CK et al. Toll-like receptor 7 mediates pruritus. Nat Neurosci. 2010; 13: 1460-1462.

18. Wang JF, Hori K, Ding J et al. Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring. J Cell Physiol. 2011; 226: 1265-1273.

19. Sato T, Yamamoto M, Shimosato T, Klinman DM. Accelerated wound healing mediated by activation of Toll-like receptor 9. Wound Repair Regen. 2010; 18: 586-593.

20. Curry JL, Qin JZ, Bonish B, Carrick R, Bacon P, Panella J. Innate immune-related receptors in normal and psoriatic skin. Arch Pathol Lab Med. 2003; 127: 178-186.

21. Kang TJ, Lee SB, Chae GT. A polymorphism in the Toll like receptor 2 is associated with IL-12 production from monocyte in lepromatous leprosy. Cytokine. 2002; 20: 56-62.

22. Krutzik SR, Ochoa MT, Sieling PA, Uematsu S, Ng YW, Legaspi A. Activation and regulation of Toll-like receptors 2 and 1 in human leprosy. Nat Med. 2003; 9: 525-532.

23. Oliveira RB, Ochoa MT, Sieling PA et al. Expression of Toll-like receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy. Infect Immun. 2003; 71: 1427-1433.

24. Kim J, Ochoa MT, Krutzik SR et al. Activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol. 2002; 169: 1535-1541.

25. Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ. Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol. 2002; 169: 1535-1541.

26. Moors MA, Li L, Mizel SB. Activation of interleukin-1 receptor-associated kinase by gram-negative flagellin. Infect Immun. 2001; 69: 4424-4429.

27. Singh SK, Girschick HJ. Toll-like receptors in Borrelia burgdorferi-induced inflammation. Clin Microbiol Infect. 2006; 12: 705-717.

28. Ahmad-Nejad P, Mrabet-Dahbi S, Breuer K, Klotz M, Werfel T. The toll-like receptor 2 R753Q polymorphism defines a subgroup of patients with atopic dermatitis having severe phenotype. J Allergy Clin Immunol. 2004; 113: 565-567.

29. Lovgren T, Eloranta ML, Bave U et al. Induction of interferon-alpha production in plasmacytoid dendritic cells by immune complexes containing nucleic acid release by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum. 2004; 50: 1861-1872.

30. Ghosh TK, Mickelson DJ, Fink J et al. Toll-like receptor(TLR) 2-9 agonists-induced cytokines and chemokines: I. Comparison with T cell receptor-induced responses. Cell Immunol. 2006; 243: 48-57.

31. Vabulas RM, Wagner H, Schild H. Heat shock proteins as ligands of toll-like receptors. Curr Top Microbiol Immunol. 2002; 270: 169-184.

32. Heil F, Ahmad-Nejad P, Hemmi H et al. The Toll-like receptor 7 (TLR7) specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily. Eur J Immunol. 2003; 3: 2987-2997.

33. Sun S, Rao NL, Venable J et al. TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007; 6: 223-235.

34. Hofmann MA, Kors C, Audring H. Phase 1 evaluation of intralesionally injected TLR9-agonist PF-3512676 in patients with basal cell carcinoma or metastatic melanoma. J Immunother. 2008; 31: 520-527.