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Increased expression of TRAIL and its death receptors DR4 and DR5 in plaque psoriasis

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Abstract

TNF-related apoptosis-inducing ligand (TRAIL) is recognized as an important regulator of immune responses during infections and various autoimmune-mediated pathologies. Its role in inflammatory dermatoses is largely unknown. We aimed to investigate the expression of TRAIL and its receptors DR4 and DR5 in psoriasis vulgaris. Immunohistochemistry for TRAIL, DR4 and DR5 was performed on samples of lesional (n = 10) and non-lesional (n = 10) skin of patients with plaque psoriasis and skin of healthy volunteers (n = 10). Expression of TRAIL and its receptors was further examined by means of double immunofluorescence staining and co-localization with CD4, CD8, CD11c, CD68, CD16 and CD56 markers. Immunohistochemical staining for TRAIL was significantly enhanced in psoriatic lesional as well as non-lesional epidermis compared to the epidermis of healthy skin. Lesional epidermis also showed increased immunoreactivity for DR5. In addition, expression of TRAIL and both of its receptors was significantly increased in the dermis of lesional skin. As evidenced by double immunofluorescence, TRAIL was readily expressed by most of the examined cells of the inflammatory infiltrate in psoriatic lesions. In contrast, the expression of DR4 was found mostly among CD4+ and CD8+ cells but was only nuclear, while DR5 showed cytoplasmic staining in rare CD16+, CD56+ and CD68+ cells. According to abundant in situ presence of TRAIL and its receptors in lesional psoriatic skin, it seems that this cytokine participates in the complex interplay between keratinocytes and cells of the dermal infiltrate and thus contributes to the inflammatory cycle in psoriasis vulgaris.

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References

  1. Bachmann F, Buechner SA, Wernli M, Strebel S, Erb P (2001) Ultraviolet light downregulates CD95 ligand and TRAIL receptor expression facilitating actinic keratosis and squamous cell carcinoma formation. J Invest Dermatol 117:59–66

    Article  PubMed  CAS  Google Scholar 

  2. Brost S, Koschny R, Sykora J, Stremmel W, Lasitschka F, Walczak H et al (2010) Differential expression of the TRAIL/TRAIL-receptor system in patients with inflammatory bowel disease. Pathol Res Pract 206:43–50

    Article  PubMed  Google Scholar 

  3. Cheung SS, Metzger DL, Wang X, Huang J, Tai J, Tingle AJ et al (2005) Tumor necrosis factor-related apoptosis-inducing ligand and CD56 expression in patients with type 1 diabetes mellitus. Pancreas 30:105–114

    Article  PubMed  CAS  Google Scholar 

  4. Collison A, Foster PS, Mattes J (2009) Emerging role of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) as a key regulator of inflammatory responses. Clin Exp Pharmacol Physiol 36:1049–1053

    Article  PubMed  CAS  Google Scholar 

  5. Falschlehner C, Emmerich CH, Gerlach B, Walczak H (2007) TRAIL signalling: decisions between life and death. Int J Biochem Cell Biol 39:1462–1475

    Article  PubMed  CAS  Google Scholar 

  6. Gilhar A, Yaniv R, Assy B, Serafimovich S, Ullmann Y, Kalish RS (2006) Fas pulls the trigger on psoriasis. Am J Pathol 168:170–175

    Article  PubMed  CAS  Google Scholar 

  7. Halaas O, Liabakk NB, Vik R, Beninati C, Henneke P, Sundan A et al (2004) Monocytes stimulated with group B streptococci or interferons release tumour necrosis factor-related apoptosis-inducing ligand. Scand J Immunol 60:74–81

    Article  PubMed  CAS  Google Scholar 

  8. Kroll TM, Bommiasamy H, Boissy RE, Hernandez C, Nickoloff BJ, Mestril R et al (2005) 4-Tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing: relevance to vitiligo. J Invest Dermatol 124:798–806

    Article  PubMed  CAS  Google Scholar 

  9. Leithner K, Stacher E, Wurm R, Ploner F, Quehenberger F, Wohlkoenig C et al (2009) Nuclear and cytoplasmic death receptor 5 as prognostic factors in patients with non-small cell lung cancer treated with chemotherapy. Lung Cancer 65:98–104

    Article  PubMed  Google Scholar 

  10. Liang Y, Yang Z, Li C, Zhu Y, Zhang L, Zhong R (2008) Characterisation of TNF-related apoptosis-inducing ligand in peripheral blood in patients with primary biliary cirrhosis. Clin Exp Med 8:1–7

    Article  PubMed  CAS  Google Scholar 

  11. Lowes MA, Bowcock AM, Krueger JG (2007) Pathogenesis and therapy of psoriasis. Nature 445:866–873

    Article  PubMed  CAS  Google Scholar 

  12. Lowes MA, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba LC, Haider AS et al (2008) Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 128:1207–1211

    Article  PubMed  CAS  Google Scholar 

  13. Mahalingam D, Szegezdi E, Keane M, Jong S, Samali A (2009) TRAIL receptor signalling and modulation: Are we on the right TRAIL? Cancer Treat Rev 35:280–288

    Article  PubMed  CAS  Google Scholar 

  14. Marble DJ, Gordon KB, Nickoloff BJ (2007) Targeting TNFalpha rapidly reduces density of dendritic cells and macrophages in psoriatic plaques with restoration of epidermal keratinocyte differentiation. J Dermatol Sci 48:87–101

    Article  PubMed  CAS  Google Scholar 

  15. Mirandola P, Ponti C, Gobbi G, Sponzilli I, Vaccarezza M, Cocco L et al (2004) Activated human NK and CD8+ T cells express both TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors but are resistant to TRAIL-mediated cytotoxicity. Blood 104:2418–2424

    Article  PubMed  CAS  Google Scholar 

  16. Nestle FO, Kaplan DH, Barker J (2009) Psoriasis. N Engl J Med 361:496–509

    Article  PubMed  CAS  Google Scholar 

  17. Nguyen V, Cudrici C, Zernetkina V, Niculescu F, Rus H, Drachenberg C et al (2009) TRAIL, DR4 and DR5 are upregulated in kidneys from patients with lupus nephritis and exert proliferative and proinflammatory effects. Clin Immunol 132:32–42

    Article  PubMed  CAS  Google Scholar 

  18. Peternel S, Kaštelan M (2009) Immunopathogenesis of psoriasis: focus on natural killer T cells. J Eur Acad Dermatol Venereol 23:1123–1127

    Article  PubMed  CAS  Google Scholar 

  19. Qin JZ, Chaturvedi V, Denning MF, Bacon P, Panella J, Choubey D et al (2002) Regulation of apoptosis by p53 in UV-irradiated human epidermis, psoriatic plaques and senescent keratinocytes. Oncogene 21:2991–3002

    Article  PubMed  CAS  Google Scholar 

  20. Ren X, Ye F, Jiang Z, Chu Y, Xiong S, Wang Y (2007) Involvement of cellular death in TRAIL/DR5-dependent suppression induced by CD4+CD25+ regulatory T cells. Cell Death Differ 14:2076–2084

    Article  PubMed  CAS  Google Scholar 

  21. Schaefer U, Voloshanenko O, Willen D, Walczak H (2007) TRAIL: a multifunctional cytokine. Front Biosci 12:3813–3824

    Article  PubMed  CAS  Google Scholar 

  22. Secchiero P, Gonelli A, Carnevale E, Corallini F, Rizzardi C, Zacchigna S et al (2004) Evidence for a proangiogenic activity of TNF-related apoptosis-inducing ligand. Neoplasia 6:364–373

    Article  PubMed  CAS  Google Scholar 

  23. Secchiero P, Zerbinati C, Rimondi E, Corallini F, Milani D, Grill V et al (2004) TRAIL promotes the survival, migration and proliferation of vascular smooth muscle cells. Cell Mol Life Sci 61:1965–1974

    Article  PubMed  CAS  Google Scholar 

  24. Stary G, Klein I, Kohlhofer S, Koszik F, Scherzer T, Müllauer L et al (2009) Plasmacytoid dendritic cells express TRAIL and induce CD4+ T-cell apoptosis in HIV-1 viremic patients. Blood 114:3854–3863

    Article  PubMed  CAS  Google Scholar 

  25. Ständer S, Schwarz T (2005) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is expressed in normal skin and cutaneous inflammatory diseases, but not in chronically UV-exposed skin and non-melanoma skin cancer. Am J Dermatopathol 27:116–121

    Article  PubMed  Google Scholar 

  26. Stegmann KA, Björkström NK, Veber H, Ciesek S, Riese P, Wiegand J et al (2010) Interferon-alpha-induced TRAIL on natural killer cells is associated with control of hepatitis C virus infection. Gastroenterology 138:1885–1897

    Article  PubMed  CAS  Google Scholar 

  27. Sun M, Fink PJ (2007) A new class of reverse signaling costimulators belongs to the TNF family. J Immunol 179:4307–4312

    PubMed  CAS  Google Scholar 

  28. Tang W, Wang W, Zhang Y, Liu S, Liu Y, Zheng D (2009) TRAIL receptor mediates inflammatory cytokine release in an NF-kappaB-dependent manner. Cell Res 19:758–767

    Article  PubMed  CAS  Google Scholar 

  29. Tchikov V, Bertsch U, Fritsch J, Edelmann B, Schütze S (2010) Subcellular compartmentalization of TNF receptor-1 and CD95 signaling pathways. Eur J Cell Biol. doi:10.1016/j.ejcb.2010.11.002

  30. Tsai HF, Lai JJ, Chou AH, Wang TF, Wu CS, Hsu PN (2004) Induction of costimulation of human CD4 T cells by tumor necrosis factor-related apoptosis-inducing ligand: possible role in T cell activation in systemic lupus erythematosus. Arthritis Rheum 50:629–639

    Article  PubMed  CAS  Google Scholar 

  31. Vassina E, Leverkus M, Yousefi S, Braathen LR, Simon HU, Simon D (2005) Increased expression and a potential anti-inflammatory role of TRAIL in atopic dermatitis. J Invest Dermatol 125:746–752

    Article  PubMed  CAS  Google Scholar 

  32. von Bubnoff D, Andrès E, Hentges F, Bieber T, Michel T, Zimmer J (2010) Natural killer cells in atopic and autoimmune diseases of the skin. J Allergy Clin Immunol 125:60–68

    Article  Google Scholar 

  33. Yang J, Li Y, Liu YQ, Long JW, Tian F, Dong J et al (2009) Expression of antiapoptotic protein c-FLIP is upregulated in psoriasis epidermis. Eur J Dermatol 19:29–33

    PubMed  Google Scholar 

  34. Yawalkar N, Tscharner GG, Hunger RE, Hassan AS (2009) Increased expression of IL-12p70 and IL-23 by multiple dendritic cell and macrophage subsets in plaque psoriasis. J Dermatol Sci 54:99–105

    Article  PubMed  CAS  Google Scholar 

  35. Zaba LC, Fuentes-Duculan J, Eungdamrong NJ, Abello MV, Novitskaya I, Pierson KC et al (2009) Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. J Invest Dermatol 129:79–88

    Article  PubMed  CAS  Google Scholar 

  36. Zaba LC, Fuentes-Duculan J, Eungdamrong NJ, Johnson-Huang LM, Nograles KE, White TR et al (2010) Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with psoriasis. J Allergy Clin Immunol 125:1261–1268.e9

    Article  PubMed  CAS  Google Scholar 

  37. Zaba LC, Krueger JG, Lowes MA (2009) Resident and “inflammatory” dendritic cells in human skin. J Invest Dermatol 129:302–308

    Article  PubMed  CAS  Google Scholar 

  38. Zauli G, Pandolfi A, Gonelli A, Di Pietro R, Guarnieri S, Ciabattoni G et al (2003) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sequentially upregulates nitric oxide and prostanoid production in primary human endothelial cells. Circ Res 92:732–740

    Article  PubMed  CAS  Google Scholar 

  39. Zhang XD, Franco AV, Nguyen T, Gray CP, Hersey P (2000) Differential localization and regulation of death and decoy receptors for TNF-related apoptosis-inducing ligand (TRAIL) in human melanoma cells. J Immunol 164:3961–3970

    PubMed  CAS  Google Scholar 

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Acknowledgments

The study was supported by Grants 062-0620239-0197 and 062-0620239-0199 of the Ministry of Science, Education and Sports of the Republic of Croatia.

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Authors and Affiliations

  1. Department of Dermatovenerology, Clinical Hospital Center Rijeka, University of Rijeka, Rijeka, Croatia

    Sandra Peternel, Larisa Prpić-Massari, Teo Manestar-Blažić, Ines Brajac & Marija Kaštelan

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  1. Sandra Peternel
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  2. Larisa Prpić-Massari
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  3. Teo Manestar-Blažić
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  4. Ines Brajac
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  5. Marija Kaštelan
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Correspondence to Sandra Peternel.

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Peternel, S., Prpić-Massari, L., Manestar-Blažić, T. et al. Increased expression of TRAIL and its death receptors DR4 and DR5 in plaque psoriasis. Arch Dermatol Res 303, 389–397 (2011). https://doi.org/10.1007/s00403-011-1125-0

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