Study of Molecular Mechanisms Involved in the Pathogenesis of Immune-Mediated Inflammatory Diseases, using Psoriasis As a Model

Cover Page
  • Authors: Piruzian ES1, Sobolev VV1, Abdeev RM2, Zolotarenko AD1, Nikolaev AA1, Sarkisova MK1, Sautin ME1, Ishkin AA1, Piruzyan A.L2, Ilyina SA2, Korsunskaya IM2, Rahimova OY3, Bruskin SA1
  • Affiliations:
    1. Vavilov Institute of General Genetics, Russian Academy of Sciences
    2. Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences
    3. Moscow Municipal Hospital № 24, Department of Health
  • Issue: Vol 1, No 3 (2009)
  • Pages: 125-135
  • Section: Articles
  • URL: http://actanaturae.ru/2075-8251/article/view/10793
  • DOI: https://doi.org/10.32607/20758251-2009-1-3-125-135
  • Cite item

Abstract


Psoriasis was used as a model to analyze the pathogenetic pathways of immune-mediated inflammatory diseases, and the results of bioinformatic, molecular-genetic and proteomic studies are provided. Cell mechanisms, common for the pathogenesis of psoriasis, as well as Crohn’s disease, are identified. New approaches for immune-mediated diseases are discussed.

Psoriasis (Psoriasis vulgaris, OMMIM 177900) is a chronic inflammatory, recurring, immune-mediated skin disease that involves several other organs and systems. Psoriasis is a complicated genetically based pathology, which involves several groups of genes [1]. The most common clinical manifestations of psoriasis are the appearance of dry, red patches of skin covered with silvery scales. The affected skin is characterized by an increase of the skin cell number and consequent inflammation due to the abnormal keratinocyte differentiation and infiltration of antigen-presenting cells, activation of T-helper cells, and release of proinflammatory cytokines [1, 2]. The appearance of “unaffected” or “uninvolved” skin is normal. However, the gene expression profiling shows that major changes happen in both damaged and undamaged skin of a psoriatic patient, as compared with the skin of a healthy individual [3]. It is supposed that the multi-gene nature of this disease is associated with the presence of several locuses, related to the susceptibility to the disease, known as PSORS1-PSORS9 (Psoriasis Susceptibility) and located on at least 9 chromosomes. Within these chromosomal regions several genes are mapped candidates to be involved in this pathological process [4-6]. In addition, the development of psoriasis may be influenced by several other genomic locuses [7-9]. According to the data appeared in 2008, candidate genes involved in the development of psoriasis may be located on 10 different locuses (PSORS1-PSORS10) [10]. A strong genetic basis of this disease has been confirmed by family and twin studies that show a high percentage of inheritance (up to 80%), as well as higher concordance (about 70%) in monozygotic twins than in dizygotic twins (up to 30%) [8]. However, just like any other multifactorial diseases, psoriasis is influenced not only by genetic factors, but also by the environment.

E S Piruzian

Vavilov Institute of General Genetics, Russian Academy of Sciences

Email: eleopiru@vigg.ru

V V Sobolev

Vavilov Institute of General Genetics, Russian Academy of Sciences

R M Abdeev

Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences

A D Zolotarenko

Vavilov Institute of General Genetics, Russian Academy of Sciences

A A Nikolaev

Vavilov Institute of General Genetics, Russian Academy of Sciences

M K Sarkisova

Vavilov Institute of General Genetics, Russian Academy of Sciences

M E Sautin

Vavilov Institute of General Genetics, Russian Academy of Sciences

A A Ishkin

Vavilov Institute of General Genetics, Russian Academy of Sciences

An L Piruzyan

Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences

S A Ilyina

Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences

I M Korsunskaya

Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences

O Y Rahimova

Moscow Municipal Hospital № 24, Department of Health

S A Bruskin

Vavilov Institute of General Genetics, Russian Academy of Sciences

  1. Lowes M.A., Bowcock A.M., Krueger J.G. Pathogenesis and therapy of psoriasis. // Nature. 2007. V. 445 P. 866–873.
  2. Bowcock A. M. and Krueger J. G. Getting under the skin: the immunogenetics of psoriasis. // Nat. Rev. Immunol. 2005. V. 5. P. 699–711.
  3. Kulsky J.K., Kenworthy W., Bellgard M. et al. Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals // J. Mol. Med. 2005. V. 85. P. 964–975.
  4. Barker J. N. Genetic aspects of psoriasis. // Clin. Exp. Dermatol. 2001. V. 26. № 4. P.321–5.
  5. Prinz J. C. Psoriasis vulgaris-a sterile antibacterial skin reaction mediated by crossreactive T cells- An immunological view of the pathophysiology of psoriasis. // Clin. Exp. Dermatol. 2001. V. 26. № 4. P. 326–32.
  6. Bowcock A. M. and Cookson W. O. The genetics of psoriasis, psoriatic arthritis and atopic dermatitis. // Hum. Mol. Genet. 2004. V. 13. № 1. P. R43–55.
  7. Asumalahti K., Veal C., Laitinen T. et al. Psoriasis Consortium. Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus. // Hum. Mol. Genet. 2002. V. 11. P. 589–597.
  8. Sagoo G.S., Cork M.J., Patel R. et al. Genome – wide studies of psoriasis susceptibility loci: a review. // Joural of Dermatological Science. 2004. V. 35. P. 171–179.
  9. Fun X., Yang S., Huang W. et al. Fine mapping of the psoriasis susceptibility locus PSORS1 support HLA-C as the susceptibility gene in the Han Chinese population. // PLoS Genet. 2008. V. 4. P. 1–10.
  10. Duffin K.C., Chandran V., Krueger G.G. et al. Genetics of Psoriasis and Psoriatic Arthritis: update and future direction (GRAPPA 2007) // J. Rheumatology. 2008. V. 35. № 7. P. 1449–1453.
  11. Duvic M., Johnson T.M., Rapini R.P. et al. Acquired immunodeficiency syndrome-associated psoriasis and Reiter’s syndrome. // Arch. Dermatol. 1987. V. 123. P. 1622–1632.
  12. Swerlick R.A., Cunningham M.W., Hall N.K. Monoclonal antibodies cross-reactive with group A streptococci and normal and psoriatic human skin. // J. Invest. Dermatol. 1986. V. 87. P. 367–371.
  13. Gold M.H., Holy A. K., Roenigk H. H. Jr. Beta-blocking drugs and psoriasis. A review of cutaneous side effects and retrospective analysis of their effects on psoriasis. // J. Am. Acad. Dermatol. 1988. V. 19. P. 837–841.
  14. Wolf R., Tamir A., Brenner S. Psoriasis related to angiotensin-converting enzyme inhibitors. // Dermatologica. 1990. V. 181. P. 51–53.
  15. Baker H. Psoriasis – clinical features. // Br. Med. 1971. V. 3. P. 231–233.
  16. Lazarus G.S., Gilgor R.S. Psoriasis, polymorphonuclear leukocytes, and lithium carbonate. An important clue. // Arch. Dermatol. 1979. V. 115. P. 1183–1184.
  17. Asumalahti K. Molecular genetics of psoriasis. // Helsinki university biomedical disseration. № 27. 2003.
  18. Sonkoly E., Wei T., Janson P.C., Saaf A. et al. MicroRN As: novel regulators involved in the pathogenesis of Psoriasis- // PLoS ONE. 2007. V. 2. № 7. P. 1–8.
  19. Yao Y., Richman L., Morehouse C. et al. Type I Interferon: Potential Therapeutic Target for Psoriasis- // PLoS One. 2008. V. 3. № 7. e2737. P. 1–14
  20. Livak K.J., Schmittgen T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. // Methods. 2001. V. 25. № 4. P.402–408.
  21. Podimov V.K., Gladkich S.P., Mishkin V.S., Piruzyan L.A., N-acetyltransferase polymorphism of patients with lupus erythematosus // “The problems of investigation, study and production of new drugs”., Shwiesa, Kaunas. – 1979, P. 52-53.
  22. Piruzyan L.A. Metabolic human passport – the basis of new strategy in pharmacology // Vestnik of RAS. 2004. V.74. P. 610-618.
  23. Piruzyan L.A. On pharmacological metrology // Bull. USSR Academy of Sci., Biol.. 1990. №2. P. 302-303.
  24. Gudjonsson J.E, Elder J.T. Psoriasis: epidemiology. // Clinics in Dermatology. 2007. V.25. P. 535–546.
  25. Piruzyan An.L., Abdeev R.M., Sarkhisova M.K. The role of pharmacogenetics and pharmacogenomics in dermatology // Clinical dermatology and venerology. 2005. №3. P. 8-13
  26. Bowcock A.M. The genetics of psoriasis and autoimmunity. // Annu. Rev. Genomics Hum. Genet. 2005. V. 6. P. 93–122.
  27. Piruzyan An.L. Doctoral diss. 2005. №3. P.352
  28. Piruzyan L.A., Goldenkova I.V., Korsunskaya I.M. et al. Scientific approach to standardization of psoriatic patient’s care (scientific review) // The problems of standardization in health care. 2006. №6. P. 7-13.
  29. Goldenkova-Pavlova I.V., Piruzyan A.L., Abdeev R.M. et. al. Population analysis and determination of the ethnic background are necessary in the study of multifactorial diseases( a study using the Dagestan population as a model) // Genetika. 2006 V.42, №8. P.1137-42.
  30. Akhmetova V.L., Galimova E.S., Yusunbaev B.B., Khusnutdinova E.K. The analysis of the genes responsible for susceptibility to psoriasis in Bashkortostan and Khakasia republics // Medical genetics. 2009. №8. P. 29-35.
  31. Bowcock A.M., Shanon W., Du F. et al. Insight into psoriasis and other inflammatory diseases from large scale gene expression studies. // Hum. Mol. Genet. 2001. V. 10. P. 1793–1805.
  32. Oestreicher J.L., Walters I.B., Kikichi T. et al. Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling. // Pharmacogenomics J. 2001. V. 1. P. 272–287.
  33. Nomura I., Gao B., Boguniewicz et al. Distinct pattern of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analisys. // J. Allegry Clin. Immunol. 2003. V. 112. P. 1195–1202.
  34. Zhou X., Krueger J.G., Као M-С.J. et al. Novel mechanism of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63, 100-element oligonucleotide array. // Physiol. Genomics. 2003. V. 13. P. 69–78.
  35. E.S. Piruzian, T.A. Nikolskaya, R.M. Abdeev, S.A. Brouskin, Transcription Factor AP-1 Components As Psoriasis Candidate Genes // Molecular Biology. 2007, Vol. 41, No.6, pp. 1069–1080.
  36. Sabat R., Philipp S., Hoflich C., et al. Immunopathogenesis of psoriasis. // Exp Dermatol. 2007. V. 16. № 10. P. 779–98.
  37. Medzhitov R., Preston-Hurlburt P., Janeway C.A. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. // Nature. 1997. V. 388. P.394–397.
  38. McInturff J.E., Modlin R.L., Kim J. The role of toll-like receptors in the pathogenesis and treatment of dermatological disease. // J. Invest Dermatol. 2005. V. 125. № 1. P. 1–8.
  39. Hu X., Chen J., Wang Lu et al. Crosstalk among Jak-STAT, Toll-like receptor, and ITAM dependent pathways in macrophage activation. // Journal of Leukocyte Biology. 2007. V. 82. P. 237–243.
  40. Schnare M., Barton G. M., Holt A. C. et al. // Nat Immunol. 2001. V.2. № 10. P. 947–950.
  41. Schjetne K.W., Thompson K.M., Nilsen N. et al. Cutting edge: link between innate and adaptive immunity: Toll-like receptor 2 internalizes antigen for presentation to CD4-T cells and could be an efficient vaccine target. // J. Immunol. 2003. V. 171. № 1. P. 32–36.
  42. Perez-Lorenzo R., Zambrano-Zaragoza J. F., Moo-Castillo K. et al. IgG class antibodies to heat shockinduced streptococcal antigens in psoriatic patients. // Int J. Dermatol. 2003. V. 42. P. 110–115.
  43. Krueger J.G. The immunologic basis for the treatment of psoriasis with new biologic agents. // J. Am. Acad. Dermatol. 2002. V. 46. № 1. P. 1–23.
  44. Reiss Y., Proudfoot A.E., Power C.A. et al. CC Chemokine Receptor (CCR )4 and the CCR 10 Ligand Cutaneous T Cell–attracting Chemokine (CT ACK) in Lymphocyte Trafficking to Inflamed Skin. // J. Exp. Med. V. 194. № 10. 2001.
  45. Lonsdorf А.S., Hwang S.T., Enk A.H.et al. Chemokine Receptors in T-Cell-Mediated Diseases of the Skin // J. Invest. Dermatol. 2009.
  46. Honey B., Alenius H., Muller A. et al. CC L27–CCR 10 interactions regulate T cellmediated skin inflammation. // Nat. Med. 2002. V. 8. P. 157–65.
  47. Chandrasekar B., Mummid S., Valente A. et al. The Pro-atherogenic Cytokine Interleukin18 Induces CXCL16 Expression in Rat Aortic Smooth Muscle Cells via MyD88, Interleukin-1 Receptor-associated Kinase, Tumor Necrosis Factor Receptor-associated Factor 6, c-Src, Phosphatidylinositol 3-Kinase, Akt, c-Jun N-terminal Kinase, and Activator Protein-1 Signaling. // The Journal of biological chemistry. 2005. V. 280. № P. 26263–26277.
  48. Turpaev K.T. 2006. Role of transcription factor AP-1 in integration of intracellular signal pathways. // Mol. Biol. 40, 945–961.
  49. Gonsky R., Deem R.L., Hughes C.C. et al. Activation of the CD2 pathway in lamina propria T cells up-regulates functionally active AP-1 binding to the IL-2 promoter, resulting in messenger RN A transcription and IL-2 secretion. // J. Immunol. 1998. V.№ 10. P. 4914–22.
  50. Bantel H., Schmitz M.L., Raible A. et al. Critical role of NF-kappaB and stress-activated protein kinases in steroid unresponsiveness. // FASEB J. 2002. V. 16. № 13. P. 1832–4.
  51. Chandrasekar B., Mummidi S., Mahimainathan L. et al. Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-kappaB- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin. // J. Biol. Chem. 2006. V. 281. № 22. P. 15099–109.
  52. Bruskin S. A. PhD Thesis, 2008. P. 120.
  53. Takeda A., Higuchi D., Takahashi T. et al. Overexpression of serpin squamous cell carcinoma antigens in psoriatic skin. // J. Invest. Dermatol. 2002. V. 118, № 1. P. 147–1454.
  54. Bruskin S.A., Abdeev R.M., Moshkovskii S.A. et. al. Psoriasis proteomic research as an approach for identification of potential targets for pharmacotherapy // Clinical dermatology and venerology. 2009. №1. P.28-31.
  55. Schreiber S., Rosenstiel P., Albrecht M. et al. Genetics of Chron disease, an archetypal inflammatory barrier disease. // Nature. 2005. V. 6. P. 376–388.
  56. Sartor B.R. Mechanisms of Disease: pathogenesis of Crohn’s disease and ulcerative colitis. // Nature Clinical Practice Gastroenterology - Hepatology. 2006. V. 3. P. 390–407.
  57. Piruzian E.S., Ishkin A.A., Nikol’Skaya T.A., Abdeev R.M., Bruskin S.A. A comparative analysis of the molecular genetic processes in the pathogenesis and Crohn’s disease, 2009, V.46, №1, P. 175-179
  58. Сhaudhari U., Romano P., Mulcahy L.D. et al. Efficacy safety of infliximab monotherapy for plaque-type psoriasis: a randomized trial. // Lancet. 2001. V. 357. P. 1842–1847.
  59. Baeten D., Kruithof E., Van den Bosch et al. Sisitematic safety follow up in a cohort of 107 patients with spondyloarthropathy treated with infliximab: a new perspective on the role of host defence in the pathogenesis of the disease- // Ann. Rheum. Dis. 2003. V.62. P. 829–834.
  60. Sfikakis P.P., Iliopopulus A., Elezoglou A. et al. Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction. // Arthritis Rheum. 2005. V. 52. P. 2513–2518.
  61. Peramiquel L., Puig L., Dalmau J. et al. Onset of flexural psoriasis during infliximab treatment for Crohn’s disease. // Clin. Exp. Dermatol. 2005. V. 30. № 6. P. 713–714.
  62. Umeno J., Matsumoto T., Jo Y. et al. Psoriasis during anti-tumor necrosis factor – alpha therapy for Crohn/s desease. // Inflamm. Bowel Dis. 2007. V. 13. P. 18188–1189.

Views

Abstract - 569

PDF (English) - 184

PDF (Russian) - 272

Cited-By


Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM

PlumX

Dimensions

Refbacks

  • There are currently no refbacks.

Copyright (c) 2009 Piruzian E.S., Sobolev V.V., Abdeev R.M., Zolotarenko A.D., Nikolaev A.A., Sarkisova M.K., Sautin M.E., Ishkin A.A., Piruzyan A.L., Ilyina S.A., Korsunskaya I.M., Rahimova O.Y., Bruskin S.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies