Molecular Mechanism Study On IL-20 And Keratin In Psoriatic Animal Model And Antisense Oligonucleotide Gene Therapy

Molecular Mechanism Study on IL-20 and Keratin in Psoriatic Animal Model and Antisense Oligonucleotide Gene TherapyPostgraduate Fan PingshenTutorLiu Yufeng ProfessorDepartment of Dermatology and Venerology,First Clinical hospital, Fourth Military Medical UniversityPsoriasis is a chronic inflammatory skin disease which is very common and easily to recur. The etiology is extremely complicated and have not been completely elucidated until now. Previous studies showed that it correlates with infection, dysfunction of endcrine system, disorder of immune function, changes of enzymes and genetic factors, etc. In recent years, many investigators think that activiation of T lymphocytes may play a pivotal role in the pathogenesis of psoriasis..T lymphocytes infiltrating to psoriatic lesions are considered as protagonist which produces many kinds of cytokines and develops a special network. Different cytokines subsequently promote epidermis to appear a psoriasis-specific hyperproliferative feature. The histopathological feature is mainly characterized by hyperproliferation of keratinocytes , gathering of inflammatory cells and vascular ectasia in dermal papillae area. The proliferation of keratinocytes is the most important feature among those .The proliferation of keratinocytes is usually accompanied by abnormal keratosis which appears parakeratosis and absent of granular layer in histological section and appears abnormalities of cytokeratin expression in biochemistry aspect. The keratin expression in normal epidermis is discribed as follows: the basal layer is mainly composed of K5/K14, the suprabasal layers is composed of K1/K10. There is a remarkable changes in keratin expression of psoriatic lesions,which is charaterized by appearance of keratins with small molecular weight insupralayers, overexpression of K14 comparing with normal epidermis.. In addition to these changes, K.1/K10, which is expressed in normal epidermis is substituted by K6/K16 which stands for hyperproliferation.The phenomena of K6, K14, K16 expression in psoriatic lesions indicate that these keratins may contain key self-epitope which can be recognised by psoriasis-specific active T lymphocytes.Among different cytokines,IL-20 is a novel one which plays a extensive modulatory role in both healthy individuals and patients with psoriasis. Previous studies showed that IL-20 could promote proliferation of keratinocytes in vitro; Overexpression of IL-20 in transgenic (TG) mice caused apparent skin abnormalities .The histopathological feature was extremely similar with psoriatic lesions.An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits designated a , P. The two subunits showed a very low expression in human normal skin,but the expression was found to be increased significantly in psoriatic lesions, which implicated that IL-20 might have an important significance in epidermis function and pathogenesis of psoriasis.To better explore the pathogenesis mechanism of psoriasis, investigators have ever established many kinds of animal models..Among these models, it is a simple and easy method that topical treatment of propranolol emulsion on ear's back of guinea pig induce poriasis-like lesions .To further explore the feasibility of this psoriatic animal model and the prospect of application study at molecular level ,our study was planed to carry out as follows: 1) Through topical treatment of 5% propranolol emulsion on ear's back of guinea pig , poriasis-like lesions were induced and psoriasis-like models of guinea pig were estabished . The reliability of this method was also confirmed. 2) Expressions of IL-20 and.keratin K.14, K16, K17 in lesions of animal models were measured. 3) Animal models were treated with antisense oligonucleotide of IL-20 or K16 and improvements of lesions were observed. 4)The feasibility of topical application with antisense oligonucleatide in treating dermatosis, including psoriasis, was also confirmed.In our experiment, 20 healthy adult guinea pi...