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

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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.

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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.
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About the authors

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

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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.

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