Korean journal of dermatology (대한피부과학회지)

Korean Dermatological Association (대한피부과학회)
권호 표지

Immunohistochemical Study of Psoriasis-related Gene Expression in Imiquimod-induced Psoriasis-like Mouse Model

이미퀴모드로 유발된 건선양 쥐 모델에서 건선 연관 유전자 발현에 대한 면역조직화학적 연구

  • Kim, Ji-Young (Department of Dermatology, Chungnam National University School of Medicine) ;
  • Choi, Mi-Ra (Department of Dermatology, Chungnam National University School of Medicine) ;
  • Choi, Chong-Won (Department of Dermatology, Chungnam National University School of Medicine) ;
  • Park, Kyung-Duck (Department of Dermatology, Chungnam National University School of Medicine) ;
  • Lee, Young (Department of Dermatology, Chungnam National University School of Medicine) ;
  • Kim, Chang-Deok (Department of Dermatology, Chungnam National University School of Medicine) ;
  • Seo, Young-Joon (Department of Dermatology, Chungnam National University School of Medicine) ;
  • Lee, Jeung-Hoon (Department of Dermatology, Chungnam National University School of Medicine)
  • 김지영 (충남대학교 의과대학 피부과학교실) ;
  • 최미라 (충남대학교 의과대학 피부과학교실) ;
  • 최종원 (충남대학교 의과대학 피부과학교실) ;
  • 박경덕 (충남대학교 의과대학 피부과학교실) ;
  • 이영 (충남대학교 의과대학 피부과학교실) ;
  • 김창덕 (충남대학교 의과대학 피부과학교실) ;
  • 서영준 (충남대학교 의과대학 피부과학교실) ;
  • 이증훈 (충남대학교 의과대학 피부과학교실)
  • Received : 2018.10.22
  • Accepted : 2018.10.26
  • Published : 2018.12.31
⟨ Previous Next ⟩

Abstract

Background: Psoriasis is a chronic inflammatory skin disease with an incidence of 0.5~3% of the worldwide population. The pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune reactions. Notably, genetic factors are considered important etiological contributors. Globally, several researchers have recently performed genome-wide association studies (GWAS) to identify the genes related with psoriasis. Objective: We aimed to investigate the expression pattern of 2 candidate genes that were identified by GWAS. These include interleukin 28 receptor alpha (IL28RA) and CUB and Sushi multiple domains 1 (CSMD1). Methods: We applied imiquimod cream to develop a psoriasis-like mouse model and obtained skin tissue. We performed immunohistochemistry to detect the expression of IL-28A and CSMD1. Results: IL28RA expression increased at an early time point such as 1 day after the topical application of 5% imiquimod cream. However, its expression returned to baseline levels 2 weeks after the topical application of imiquimod cream. CSMD1 expression also increased after the topical application of imiquimod, with increased expression particularly observed in the upper epidermal layer. Notably, CSMD1 expression decreased 7 days after imiquimod cream application. Conclusion: These results suggest that IL28RA and CSMD1 may play key roles in the pathogenesis of psoriasis.

Keywords

Acknowledgement

Supported by : 한국연구재단

References

  1. Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol 2017;140:645-653 https://doi.org/10.1016/j.jaci.2017.07.004
  2. Lowes MA, Russell CB, Martin DA, Towne JE, Krueger JG. The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol 2013;34:174-181 https://doi.org/10.1016/j.it.2012.11.005
  3. Kim J, Krueger JG. Highly effective new treatments for psoriasis target the IL-23/Type 17 T cell autoimmune axis. Annu Rev Med 2017;68:255-269 https://doi.org/10.1146/annurev-med-042915-103905
  4. Generali E, Ceribelli A, Stazi MA, Selmi C. Lessons learned from twins in autoimmune and chronic inflammatory diseases. J Autoimmun 2017;83:51-61 https://doi.org/10.1016/j.jaut.2017.04.005
  5. Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2, Strange A, Capon F, Spencer CC, Knight J, Weale ME, et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 2010;42:985-990 https://doi.org/10.1038/ng.694
  6. Chandran V. The genetics of psoriasis and psoriatic arthritis. Clin Rev Allergy Immunol 2013;44:149-156 https://doi.org/10.1007/s12016-012-8303-5
  7. van der Fits L, Mourits S, Voerman JS, Kant M, Boon L, Laman JD, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol 2009;182:5836-5845 https://doi.org/10.4049/jimmunol.0802999
  8. Griffiths SJ, Dunnigan CM, Russell CD, Haas JG. The role of interferon-$\lambda$ locus polymorphisms in hepatitis C and other infectious diseases. J Innate Immun 2015;7:231-242 https://doi.org/10.1159/000369902
  9. Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, et al. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 2003;4:69-77
  10. Lopez de Lapuente A, Alloza I, Goertsches R, Zettl UK, Urcelay E, Arroyo R, et al. Analysis of the IL28RA locus as genetic risk factor for multiple sclerosis. J Neuroimmunol 2012;245:98-101 https://doi.org/10.1016/j.jneuroim.2012.02.005
  11. Li Y, Cheng H, Zuo XB, Sheng YJ, Zhou FS, Tang XF, et al. Association analyses identifying two common susceptibility loci shared by psoriasis and systemic lupus erythematosus in the Chinese Han population. J Med Genet 2013;50:812-818 https://doi.org/10.1136/jmedgenet-2013-101787
  12. Lebre MC, van der Aar AM, van Baarsen L, van Capel TM, Schuitemaker JH, Kapsenberg ML, et al. Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9. J Invest Dermatol 2007;127:331-341 https://doi.org/10.1038/sj.jid.5700530
  13. Prens EP, Kant M, van Dijk G, van der Wel LI, Mourits S, van der Fits L. $IFN-{\alpha}$ enhances poly-IC responses in human keratinocytes by inducing expression of cytosolic innate RNA receptors: relevance for psoriasis. J Invest Dermatol 2008;128:932-938 https://doi.org/10.1038/sj.jid.5701087
  14. Chen X, Takai T, Xie Y, Niyonsaba F, Okumura K, Ogawa H. Human antimicrobial peptide LL-37 modulates proinflammatory responses induced by cytokine milieus and double-stranded RNA in human keratinocytes. Biochem Biophys Res Commun 2013;433:532-537 https://doi.org/10.1016/j.bbrc.2013.03.024
  15. Sun PC, Uppaluri R, Schmidt AP, Pashia ME, Quant EC, Sunwoo JB, et al. Transcript map of the 8p23 putative tumor suppressor region. Genomics 2001;75:17-25 https://doi.org/10.1006/geno.2001.6587
  16. Ma C, Quesnelle KM, Sparano A, Rao S, Park MS, Cohen MA, et al. Characterization CSMD1 in a large set of primary lung, head and neck, breast and skin cancer tissues. Cancer Biol Ther 2009;8:907-916 https://doi.org/10.4161/cbt.8.10.8132
  17. Tang MR, Wang YX, Guo S, Han SY, Wang D. CSMD1 exhibits antitumor activity in A375 melanoma cells through activation of the Smad pathway. Apoptosis 2012;17:927-937 https://doi.org/10.1007/s10495-012-0727-0
  18. Kamal M, Holliday DL, Morrison EE, Speirs V, Toomes C, Bell SM. Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion. Oncol Rep 2017;38:283-292 https://doi.org/10.3892/or.2017.5656