Skip to main content
Top
Published in: Archives of Dermatological Research 9/2012

01-11-2012 | Original Paper

Assessment of an imiquimod-induced psoriatic mouse model in relation to oxidative stress

Authors: Jin-Ok Baek, Dashlkhumbe Byamba, Wen Hao Wu, Tae-Gyun Kim, Min-Geol Lee

Published in: Archives of Dermatological Research | Issue 9/2012

Login to get access

Abstract

Psoriasis is a chronic inflammatory skin disease that is thought to be related to oxidative stress. Much progress has been made in understanding the pathophysiology of psoriasis in relation to the immunologic and antioxidant systems. However, this progress has been hindered by the lack of an appropriate animal model for psoriasis. Recently, imiquimod (IQM)-induced psoriasis-like cutaneous inflammation has been reported in mice and humans. We verified the usefulness of an IQM-induced mouse model in relation to the antioxidant system. BALB/C female mice at 8–10 weeks of age were treated with IQM cream in this study. We analyzed clinical and histopathological changes. Increased reactive oxygen species production was measured by glutathione assay. Levels of myeloperoxidase (MPO) and superoxide dismutase-1 (SOD1) were determined by western blotting and immunohistochemical analyses. The activity of SOD was measured by a SOD activity assay kit. Application of IQM-induced skin inflammation similar to psoriasis in clinical and histopathological aspects. Accumulation of immune cells was confirmed. Oxidative stress was increased, the antioxidant enzyme MPO levels were increased, and both SOD levels and activity were decreased. In conclusion, the IQM-induced mouse model showed an aberrant antioxidant system. Levels of MPO and oxidative stress were increased, and the level and activity of SOD were decreased. Since this model seemed to be an appropriate model for psoriasis, it can be used to further study the pathogenic role of redox imbalance in psoriasis.
Literature
1.
go back to reference Ardavin C (2003) Origin, precursors and differentiation of mouse dendritic cells. Nat Rev Immunol 3(7):582–590PubMedCrossRef Ardavin C (2003) Origin, precursors and differentiation of mouse dendritic cells. Nat Rev Immunol 3(7):582–590PubMedCrossRef
2.
go back to reference Berking C, Takemoto R, Binder RL, Hartman SM, Ruiter DJ, Gallagher PM, Lessin SR, Herlyn M (2002) Photocarcinogenesis in human adult skin grafts. Carcinogenesis 23(1):181–187PubMedCrossRef Berking C, Takemoto R, Binder RL, Hartman SM, Ruiter DJ, Gallagher PM, Lessin SR, Herlyn M (2002) Photocarcinogenesis in human adult skin grafts. Carcinogenesis 23(1):181–187PubMedCrossRef
3.
go back to reference Bhagavathula N, Nerusu KC, Fisher GJ, Liu G, Thakur AB, Gemmell L, Kumar S, Xu ZH, Hinton P, Tsurushita N, Landolfi NF, Voorhees JJ, Varani J (2005) Amphiregulin and epidermal hyperplasia: amphiregulin is required to maintain the psoriatic phenotype of human skin grafts on severe combined immunodeficient mice. Am J Pathol 166(4):1009–1016PubMedCrossRef Bhagavathula N, Nerusu KC, Fisher GJ, Liu G, Thakur AB, Gemmell L, Kumar S, Xu ZH, Hinton P, Tsurushita N, Landolfi NF, Voorhees JJ, Varani J (2005) Amphiregulin and epidermal hyperplasia: amphiregulin is required to maintain the psoriatic phenotype of human skin grafts on severe combined immunodeficient mice. Am J Pathol 166(4):1009–1016PubMedCrossRef
4.
go back to reference Conrad C, Nestle FO (2006) Animal models of psoriasis and psoriatic arthritis: an update. Curr Rheumatol Rep 8(5):342–347PubMedCrossRef Conrad C, Nestle FO (2006) Animal models of psoriasis and psoriatic arthritis: an update. Curr Rheumatol Rep 8(5):342–347PubMedCrossRef
5.
6.
go back to reference De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O (2000) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 192(7):1069–1074CrossRef De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O (2000) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 192(7):1069–1074CrossRef
7.
go back to reference Dogan P, Soyuer U, Tanrikulu G (1989) Superoxide dismutase and myeloperoxidase activity in polymorphonuclear leukocytes, and serum ceruloplasmin and copper levels, in psoriasis. Br J Dermatol 120(2):239–244PubMedCrossRef Dogan P, Soyuer U, Tanrikulu G (1989) Superoxide dismutase and myeloperoxidase activity in polymorphonuclear leukocytes, and serum ceruloplasmin and copper levels, in psoriasis. Br J Dermatol 120(2):239–244PubMedCrossRef
8.
go back to reference Dorschner RA, Pestonjamasp VK, Tamakuwala S, Ohtake T, Rudisill J, Nizet V, Agerberth B, Gudmundsson GH, Gallo RL (2001) Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. J Invest Dermatol 117(1):91–97PubMedCrossRef Dorschner RA, Pestonjamasp VK, Tamakuwala S, Ohtake T, Rudisill J, Nizet V, Agerberth B, Gudmundsson GH, Gallo RL (2001) Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. J Invest Dermatol 117(1):91–97PubMedCrossRef
9.
go back to reference Gabr SA, Al-Ghadir AH (2012) Role of cellular oxidative stress and cytochrome c in the pathogenesis of psoriasis. Arch Dermatol Res 304(6):451–457 Gabr SA, Al-Ghadir AH (2012) Role of cellular oxidative stress and cytochrome c in the pathogenesis of psoriasis. Arch Dermatol Res 304(6):451–457
10.
go back to reference Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, Homey B, Barrat FJ, Zal T, Gilliet M (2009) Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med 206(9):1983–1994PubMedCrossRef Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, Homey B, Barrat FJ, Zal T, Gilliet M (2009) Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med 206(9):1983–1994PubMedCrossRef
11.
go back to reference Gerbaud P, Petzold L, Therond P, Anderson WB, Evain-Brion D, Raynaud F (2005) Differential regulation of Cu, Zn- and Mn-superoxide dismutases by retinoic acid in normal and psoriatic human fibroblasts. J Autoimmun 24(1):69–78PubMedCrossRef Gerbaud P, Petzold L, Therond P, Anderson WB, Evain-Brion D, Raynaud F (2005) Differential regulation of Cu, Zn- and Mn-superoxide dismutases by retinoic acid in normal and psoriatic human fibroblasts. J Autoimmun 24(1):69–78PubMedCrossRef
12.
go back to reference Gilliet M, Conrad C, Geiges M, Cozzio A, Thurlimann W, Burg G, Nestle FO, Dummer R (2004) Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors. Arch Dermatol 140(12):1490–1495PubMedCrossRef Gilliet M, Conrad C, Geiges M, Cozzio A, Thurlimann W, Burg G, Nestle FO, Dummer R (2004) Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors. Arch Dermatol 140(12):1490–1495PubMedCrossRef
13.
go back to reference Godfrey DI, Hammond KJ, Poulton LD, Smyth MJ, Baxter AG (2000) NKT cells: facts, functions and fallacies. Immunol Today 21(11):573–583PubMedCrossRef Godfrey DI, Hammond KJ, Poulton LD, Smyth MJ, Baxter AG (2000) NKT cells: facts, functions and fallacies. Immunol Today 21(11):573–583PubMedCrossRef
14.
go back to reference Gudjonsson JE, Johnston A, Dyson M, Valdimarsson H, Elder JT (2007) Mouse models of psoriasis. J Invest Dermatol 127(6):1292–1308PubMedCrossRef Gudjonsson JE, Johnston A, Dyson M, Valdimarsson H, Elder JT (2007) Mouse models of psoriasis. J Invest Dermatol 127(6):1292–1308PubMedCrossRef
15.
go back to reference Kharaeva Z, Gostova E, De Luca C, Raskovic D, Korkina L (2009) Clinical and biochemical effects of coenzyme Q (10), vitamin E, and selenium supplementation to psoriasis patients. Nutrition 25(3):295–302PubMedCrossRef Kharaeva Z, Gostova E, De Luca C, Raskovic D, Korkina L (2009) Clinical and biochemical effects of coenzyme Q (10), vitamin E, and selenium supplementation to psoriasis patients. Nutrition 25(3):295–302PubMedCrossRef
16.
go back to reference Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Wang YH, Su B, Nestle FO, Zal T, Mellman I, Schroder JM, Liu YJ, Gilliet M (2007) Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449(7162):564–569PubMedCrossRef Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Wang YH, Su B, Nestle FO, Zal T, Mellman I, Schroder JM, Liu YJ, Gilliet M (2007) Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449(7162):564–569PubMedCrossRef
17.
go back to reference Lowes MA, Bowcock AM, Krueger JG (2007) Pathogenesis and therapy of psoriasis. Nature 445(7130):866–873PubMedCrossRef Lowes MA, Bowcock AM, Krueger JG (2007) Pathogenesis and therapy of psoriasis. Nature 445(7130):866–873PubMedCrossRef
18.
go back to reference Miyachi Y, Niwa Y (1983) Effects of psoriatic sera on the generation of oxygen intermediates by normal polymorphonuclear leucocytes. Arch Dermatol Res 275(1):23–26PubMedCrossRef Miyachi Y, Niwa Y (1983) Effects of psoriatic sera on the generation of oxygen intermediates by normal polymorphonuclear leucocytes. Arch Dermatol Res 275(1):23–26PubMedCrossRef
19.
go back to reference Nagaoka I, Tamura H, Hirata M (2006) An antimicrobial cathelicidin peptide, human CAP18/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7. J Immunol 176(5):3044–3052PubMed Nagaoka I, Tamura H, Hirata M (2006) An antimicrobial cathelicidin peptide, human CAP18/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7. J Immunol 176(5):3044–3052PubMed
20.
go back to reference Nelson KC, Carlson JL, Newman ML, Sternberg P Jr, Jones DP, Kavanagh TJ, Diaz D, Cai J, Wu M (1999) Effect of dietary inducer dimethylfumarate on glutathione in cultured human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 40(9):1927–1935PubMed Nelson KC, Carlson JL, Newman ML, Sternberg P Jr, Jones DP, Kavanagh TJ, Diaz D, Cai J, Wu M (1999) Effect of dietary inducer dimethylfumarate on glutathione in cultured human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 40(9):1927–1935PubMed
21.
go back to reference Nestle FO, Conrad C, Tun-Kyi A, Homey B, Gombert M, Boyman O, Burg G, Liu YJ, Gilliet M (2005) Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med 202(1):135–143PubMedCrossRef Nestle FO, Conrad C, Tun-Kyi A, Homey B, Gombert M, Boyman O, Burg G, Liu YJ, Gilliet M (2005) Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med 202(1):135–143PubMedCrossRef
22.
go back to reference Nickoloff BJ, Wrone-Smith T (1999) Injection of pre-psoriatic skin with CD4+ T cells induces psoriasis. Am J Pathol 155(1):145–158PubMedCrossRef Nickoloff BJ, Wrone-Smith T (1999) Injection of pre-psoriatic skin with CD4+ T cells induces psoriasis. Am J Pathol 155(1):145–158PubMedCrossRef
23.
go back to reference Nickoloff BJ, Xin H, Nestle FO, Qin JZ (2007) The cytokine and chemokine network in psoriasis. Clin Dermatol 25(6):568–573PubMedCrossRef Nickoloff BJ, Xin H, Nestle FO, Qin JZ (2007) The cytokine and chemokine network in psoriasis. Clin Dermatol 25(6):568–573PubMedCrossRef
24.
go back to reference Nikolic-Kokic A, Stevic Z, Blagojevic D, Davidovic B, Jones DR, Spasic MB (2006) Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients. Clin Chem Lab Med 44(5):589–593PubMedCrossRef Nikolic-Kokic A, Stevic Z, Blagojevic D, Davidovic B, Jones DR, Spasic MB (2006) Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients. Clin Chem Lab Med 44(5):589–593PubMedCrossRef
25.
go back to reference Palamara F, Meindl S, Holcmann M, Luhrs P, Stingl G, Sibilia M (2004) Identification and characterization of pDC-like cells in normal mouse skin and melanomas treated with imiquimod. J Immunol 173(5):3051–3061PubMed Palamara F, Meindl S, Holcmann M, Luhrs P, Stingl G, Sibilia M (2004) Identification and characterization of pDC-like cells in normal mouse skin and melanomas treated with imiquimod. J Immunol 173(5):3051–3061PubMed
26.
go back to reference Patel U, Mark NM, Machler BC, Levine VJ (2011) Imiquimod 5 % cream induced psoriasis: a case report, summary of the literature and mechanism. Br J Dermatol 164(3):670–672PubMed Patel U, Mark NM, Machler BC, Levine VJ (2011) Imiquimod 5 % cream induced psoriasis: a case report, summary of the literature and mechanism. Br J Dermatol 164(3):670–672PubMed
27.
go back to reference Popov I, Lewin G (1991) A deficient function of the antioxidative system of the organism as an aetiopathogenetic factor in psoriasis. Med Hypotheses 35(3):229–236PubMedCrossRef Popov I, Lewin G (1991) A deficient function of the antioxidative system of the organism as an aetiopathogenetic factor in psoriasis. Med Hypotheses 35(3):229–236PubMedCrossRef
28.
go back to reference Portugal M, Barak V, Ginsburg I, Kohen R (2007) Interplay among oxidants, antioxidants, and cytokines in skin disorders: present status and future considerations. Biomed Pharmacother 61(7):412–422PubMedCrossRef Portugal M, Barak V, Ginsburg I, Kohen R (2007) Interplay among oxidants, antioxidants, and cytokines in skin disorders: present status and future considerations. Biomed Pharmacother 61(7):412–422PubMedCrossRef
29.
go back to reference Rajan N, Langtry JA (2006) Generalized exacerbation of psoriasis associated with imiquimod cream treatment of superficial basal cell carcinomas. Clin Exp Dermatol 31(1):140–141PubMedCrossRef Rajan N, Langtry JA (2006) Generalized exacerbation of psoriasis associated with imiquimod cream treatment of superficial basal cell carcinomas. Clin Exp Dermatol 31(1):140–141PubMedCrossRef
30.
go back to reference Raynaud F, Evain-Brion D, Gerbaud P, Marciano D, Gorin I, Liapi C, Anderson WB (1997) Oxidative modulation of cyclic AMP-dependent protein kinase in human fibroblasts: possible role in psoriasis. Free Radic Biol Med 22(4):623–632PubMedCrossRef Raynaud F, Evain-Brion D, Gerbaud P, Marciano D, Gorin I, Liapi C, Anderson WB (1997) Oxidative modulation of cyclic AMP-dependent protein kinase in human fibroblasts: possible role in psoriasis. Free Radic Biol Med 22(4):623–632PubMedCrossRef
31.
go back to reference Schon MP, Schon M, Klotz KN (2006) The small antitumoral immune response modifier imiquimod interacts with adenosine receptor signaling in a TLR7- and TLR8-independent fashion. J Invest Dermatol 126(6):1338–1347PubMedCrossRef Schon MP, Schon M, Klotz KN (2006) The small antitumoral immune response modifier imiquimod interacts with adenosine receptor signaling in a TLR7- and TLR8-independent fashion. J Invest Dermatol 126(6):1338–1347PubMedCrossRef
32.
go back to reference Shen T, Zhu QX, Yang S, Wu CH, Zhang HF, Zhou CF, Zhang XJ (2008) Trichloroethylene induced cutaneous irritation in BALB/c hairless mice: histopathological changes and oxidative damage. Toxicology 248(2–3):113–120PubMedCrossRef Shen T, Zhu QX, Yang S, Wu CH, Zhang HF, Zhou CF, Zhang XJ (2008) Trichloroethylene induced cutaneous irritation in BALB/c hairless mice: histopathological changes and oxidative damage. Toxicology 248(2–3):113–120PubMedCrossRef
33.
go back to reference Swindell WR, Johnston A, Carbajal S, Han G, Wohn C, Lu J, Xing X, Nair RP, Voorhees JJ, Elder JT, Wang XJ, Sano S, Prens EP, DiGiovanni J, Pittelkow MR, Ward NL, Gudjonsson JE (2011) Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis. PloS one 6(4):e18266PubMedCrossRef Swindell WR, Johnston A, Carbajal S, Han G, Wohn C, Lu J, Xing X, Nair RP, Voorhees JJ, Elder JT, Wang XJ, Sano S, Prens EP, DiGiovanni J, Pittelkow MR, Ward NL, Gudjonsson JE (2011) Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis. PloS one 6(4):e18266PubMedCrossRef
34.
go back to reference Therond P, Gerbaud P, Dimon S, Anderson WB, Evain-Broin D, Raynaud F (1996) Antioxidant enzymes in psoriatic fibroblasts and erythrocytes. J Invest Dermatol 106(6):1325–1328PubMedCrossRef Therond P, Gerbaud P, Dimon S, Anderson WB, Evain-Broin D, Raynaud F (1996) Antioxidant enzymes in psoriatic fibroblasts and erythrocytes. J Invest Dermatol 106(6):1325–1328PubMedCrossRef
35.
go back to reference Thiele JJ, Schroeter C, Hsieh SN, Podda M, Packer L (2001) The antioxidant network of the stratum corneum. Curr Probl Dermatol 29:26–42PubMedCrossRef Thiele JJ, Schroeter C, Hsieh SN, Podda M, Packer L (2001) The antioxidant network of the stratum corneum. Curr Probl Dermatol 29:26–42PubMedCrossRef
36.
go back to reference Utas S, Kose K, Yazici C, Akdas A, Kelestimur F (2002) Antioxidant potential of propylthiouracil in patients with psoriasis. Clin Biochem 35(3):241–246PubMedCrossRef Utas S, Kose K, Yazici C, Akdas A, Kelestimur F (2002) Antioxidant potential of propylthiouracil in patients with psoriasis. Clin Biochem 35(3):241–246PubMedCrossRef
37.
go back to reference van der Fits L, Mourits S, Voerman JS, Kant M, Boon L, Laman JD, Cornelissen F, Mus AM, Florencia E, Prens EP, Lubberts E (2009) Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol 182(9):5836–5845PubMedCrossRef van der Fits L, Mourits S, Voerman JS, Kant M, Boon L, Laman JD, Cornelissen F, Mus AM, Florencia E, Prens EP, Lubberts E (2009) Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol 182(9):5836–5845PubMedCrossRef
38.
go back to reference Vanizor Kural B, Orem A, Cimsit G, Yandi YE, Calapoglu M (2003) Evaluation of the atherogenic tendency of lipids and lipoprotein content and their relationships with oxidant-antioxidant system in patients with psoriasis. Clin Chim Acta 328(1–2):71–82PubMedCrossRef Vanizor Kural B, Orem A, Cimsit G, Yandi YE, Calapoglu M (2003) Evaluation of the atherogenic tendency of lipids and lipoprotein content and their relationships with oxidant-antioxidant system in patients with psoriasis. Clin Chim Acta 328(1–2):71–82PubMedCrossRef
39.
go back to reference Wierinckx A, Breve J, Mercier D, Schultzberg M, Drukarch B, Van Dam AM (2005) Detoxication enzyme inducers modify cytokine production in rat mixed glial cells. J Neuroimmunol 166(1–2):132–143PubMedCrossRef Wierinckx A, Breve J, Mercier D, Schultzberg M, Drukarch B, Van Dam AM (2005) Detoxication enzyme inducers modify cytokine production in rat mixed glial cells. J Neuroimmunol 166(1–2):132–143PubMedCrossRef
40.
go back to reference Young CN, Koepke JI, Terlecky LJ, Borkin MS, Boyd Savoy L, Terlecky SR (2008) Reactive oxygen species in tumor necrosis factor-alpha-activated primary human keratinocytes: implications for psoriasis and inflammatory skin disease. J Invest Dermatol 128(11):2606–2614PubMedCrossRef Young CN, Koepke JI, Terlecky LJ, Borkin MS, Boyd Savoy L, Terlecky SR (2008) Reactive oxygen species in tumor necrosis factor-alpha-activated primary human keratinocytes: implications for psoriasis and inflammatory skin disease. J Invest Dermatol 128(11):2606–2614PubMedCrossRef
41.
go back to reference Zheng Y, Niyonsaba F, Ushio H, Nagaoka I, Ikeda S, Okumura K, Ogawa H (2007) Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human alpha-defensins from neutrophils. Br J Dermatol 157(6):1124–1131PubMedCrossRef Zheng Y, Niyonsaba F, Ushio H, Nagaoka I, Ikeda S, Okumura K, Ogawa H (2007) Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human alpha-defensins from neutrophils. Br J Dermatol 157(6):1124–1131PubMedCrossRef
42.
go back to reference Zhou Q, Mrowietz U, Rostami-Yazdi M (2009) Oxidative stress in the pathogenesis of psoriasis. Free Radic Biol Med 47(7):891–905PubMedCrossRef Zhou Q, Mrowietz U, Rostami-Yazdi M (2009) Oxidative stress in the pathogenesis of psoriasis. Free Radic Biol Med 47(7):891–905PubMedCrossRef
Metadata
Title
Assessment of an imiquimod-induced psoriatic mouse model in relation to oxidative stress
Authors
Jin-Ok Baek
Dashlkhumbe Byamba
Wen Hao Wu
Tae-Gyun Kim
Min-Geol Lee
Publication date
01-11-2012
Publisher
Springer-Verlag
Published in
Archives of Dermatological Research / Issue 9/2012
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-012-1272-y

Other articles of this Issue 9/2012

Archives of Dermatological Research 9/2012 Go to the issue